HU192451B - Process for preparing alpha-sulphonyl-oxy- ketone-acetal derivatives - Google Patents

Abstract

The present invention relates to a process for the preparation of the α-sulphonyloxy-ketone acetal derivatives of the formula (II): wherein Ar is chloro or fluoro, C 1 -C 4 alkyl, phenyl, acetamide, 2 halogens. optionally substituted phenyl having 1 to 4 carbon atoms or 1-oxo-2-isoindolinyl optionally substituted with phenyl, and 2-thienyl or 6-methoxy-2-naphthyl; - R 1 is hydrogen or C 1-4 alkyl; or - Ar and R 1 together may represent 1,2,3,4-tetrahydronaphthyl; - R3 and R4 are independently 1- (C4-alkyl or C2-C6-alkylene, -R5 is C1-C4-alkyl, phenyl, C1-C4-alkyl) -phenyl, halo-phenyl- or d- or 1-10 camphor. OR3 I Ar - C - Cl4 p ~ r5 CH - R -1 -1-

Description

The present invention relates to novel a-sulfonyloxy-ketone acetal derivatives of the general formula (II). These compounds serve as starting materials for the preparation of alkanoic acids having an aromatic group at the α-position of formula I and their esters.

In the formula (II):

Ar is phenyl optionally substituted with chloro or fluoro, C 1-4 alkyl, phenyl, acetamido, C 1-4 alkoxy optionally substituted with 2 halogens, or 1-oxo-2-isoindolinyl, and 2-thienyl; or 6-methoxy-2-naphthyl;

- R ¹ is hydrogen or

C 1-4 alkyl; or - Ar and R ^{1 taken} together are 1,2,3,4-tetrahydronaphthyl;

- R ³ and R ⁴ are each independently

C 1 -C 4 alkyl or C 2 -C 6 alkylene together;

R ⁵ is C 1-4 alkyl, phenyl, (C 1-4 alkyl) phenyl, halophenyl or d or 1-10 camphoryl.

The compounds of formula (I) are useful as starting materials for pyrethroid insecticides and are useful in medicine. In the formula (I), Ar, R ¹ and R ² are as defined above.

Compounds of formula (II) are prepared by:

a) Compound of formula V - X is halogen, Ar and R ¹ are as defined above - R ³ OM is an alkali metal alkoxide - R ³ is as defined above and M is an alkali metal atom in the presence of alcohol R ³ OH - R ³ is as defined above; obsession

b) reacting a compound of formula V with Ar, X and R ¹ as defined above, with an alkali metal alkoxide R ³ OM, with R ³ and M as above, and then reacting the resulting epoxy compound VII with Ar. R ¹ and R ³ are as defined above for reaction with an alcohol of formula R ⁴ OH; R ⁴ is as defined above for R ⁴ OM in the presence of an alkali metal alkoxide; R ⁴ and M are as defined above; obsession

c) reacting the compound of formula V - Ar, X and R ¹ is as defined above - with alkylene glycol and then obtaining the compound of formula VI - Ar, R ¹ , R ³ and R ⁴ as defined above - R ⁵ - compound of the formula SO2-Hal or ^(R5 -SO2) 2 O - R ⁵ are as defined and Hal have the meanings as is halogen, is reacted.

The present invention also includes the hydrolysis of a-sulfonyloxy-ketone acetal of formula II.

It has been found that the hydrolysis of the compound of formula (II) results in a special reaction in which the sulfonyloxy group in position 2 is cleaved and the aromatic group in position 1 is converted to position 2; This gives the t-alkanoic acid of formula (I) substituted at the α-position by an aromatic group.

The hydrolysis may be carried out in the absence of a solvent, but it is preferable to carry out the reaction in an inert solvent. Suitable inert solvents include proton-free, polar solvents such as dimethylformamide (DMF), dimethylsulfoxide (DMSO), 1,3-dimethyl-2-imidazolidinone (DMI), 1,4-dioxane, tetrahydrofuran (THF), diethylene glycol dimethyl ether (diglyme), hexamethylphosphoric triamide (HMPA), 1,2-dimethoxyethane and pyridine; polar solvents include methanol, ethanol, ethylene glycol and acetic acid. The solvents are used singly or in combination.

The reaction temperature is not critical and may vary widely depending on the nature of the starting material. In general, the reaction is carried out at 0 to 250 ° C, preferably at room temperature to 200 ° C. It is convenient to choose a higher temperature to facilitate the reaction, generally between 40 ° C and the boiling point, and preferably between 50 ° C and 180 ° C. The reaction can be conducted under atmospheric pressure or at elevated pressure.

The water required for the hydrolysis of the compounds of formula (II) is introduced at the beginning of the operation by mixing with the solvent and adding the compound (II) to the solvent. Alternatively, the process may be reversed by adding the compound of formula (II) to the solvent, and then adding the required amount of water to the resulting solution.

Alternatively, the compound of formula (II) is heated to the desired temperature in the presence of anhydrous solvent and then the required amount of water is added (Examples 31 and 35).

The simplest solution is to add the compound of formula II to a mixture of water and a polar solvent.

The hydrolysis is 2; the amount of water required is not critical and depends on the nature of the compound of formula (II), the reaction conditions, etc. Generally, at least 1 mol of water, preferably at least 5 mol, of water is used per compound of formula (II). If the amount of water used is too high, the solubility of the compound of formula II will decrease. It is therefore advisable to keep the amount of water within limits.

The acetal moiety on the compound of formula (II) is a non-acidic non-acid-forming compound

Hydrolysis is generally carried out under neutral or basic conditions at pHs 7-14 to prevent 192,451 ruptures.

Since the sulfonyloxy group (-OSO ₂ -R ⁵ ) in position _{2 is} cleaved as the sulfonic acid (R ⁵ SO ₃ H) by hydrolysis, it is preferable to carry out the reaction in the presence of an alkali, it is kept in a neutral or alkaline range. Useful bases include alkali metal hydroxides such as potassium or sodium hydroxide; alkaline earth metal hydroxides such as magnesium hydroxide and calcium hydroxide; alkali metal carbonates such as potassium carbonate and sodium carbonate; alkaline earth metal carbonates such as magnesium and calcium carbonate; alkali metal bicarbonates such as potassium and sodium bicarbonate; alkali metal carboxylates such as sodium formic acid, sodium acetate, potassium acetate, sodium propionate; alkali metal phosphates such as sodium and potassium phosphate; organic tertiary amines such as pyridine, triethylamine, tributylamine. These inorganic or organic bases are preferably used in an amount of at least one equivalent, preferably from 1 to 10 equivalents, per mole of the compound of formula (II).

The hydrolysis generally takes from 1 to 250 hours, but the reaction time is highly dependent on the nature of the compounds of formula II and the reaction conditions.

During hydrolysis, the sulfonyloxy group in the 2-position is removed from the compound of formula II, while the aromatic group in the 1-position is converted to the 2-position. However, one of the acetal groups OR ³ and OR * is separated, the remaining acetal group will form the OR ² group in the resulting compound of formula I (where R ² is alkyl). Depending on the conditions of hydrolysis, especially under very basic conditions, the resulting ester compound of formula I (R ² is alkyl) may be further hydrolyzed to give compounds of formula I wherein R ² is hydrogen.

When R ³ and R ^{4 taken} together in the compound of formula (II) form an alkylene group and this compound is hydrolyzed, a compound of formula (I) wherein R ² is hydroxyalkyl is obtained.

In another embodiment of the present invention, compounds of formula II are treated with an agent that is capable of binding oxygen. In this embodiment, it has been found that the compound of formula II is cleaved at the 2-position (-OSO ₂ -R ⁵ ) and the aromatic at the 1-position is shifted to the 2-position. The reaction gives a compound of formula (I). One of the groups OR ³ and OR ⁴ will form OR ^{2 in} the compound of formula (I). When R ² is alkyl in formula I, the reaction product is an ester.

The term "oxygen scavenger compound" refers to a derivative capable of binding a free electron pair of an oxygen atom. Among the compounds capable of oxygen scavenging are the following:

(a) The iodo-trialkylsilanes of formula (III) wherein A ¹ , A ² and A ³ are the same or different C 1-4 alkyl groups such as iodotetrimethylsilane or iodo-triethylsilane.

(b) the trialkylsilyl perfluoroalkyl sulfonates of formula (IV) wherein A ⁴ is a perfluoro (C 1 -C 4 alkyl) group and A ¹ , A ² and A ³ are as defined above; such as trimethylsilyl trifluoromethanesulfonate, trimethylsilyl pentafluoroethane sulfonate.

(c) Lewis acids such as aluminum chloride, aluminum bromide, zinc chloride, lead chloride, titanium chloride, boron fluoride and ferric chloride.

These compounds are capable of oxygen JCffegr. knit, individually or in combination. Particularly preferred are iodine trimethylsilane, trimethylsil trifluoromethanesulfonate, ferric chloride, aluminum chloride and tin chloride.

The amount of oxygen scavenger used is not strictly defined and may vary according to the type of compound of formula II and the type of oxygen scavenger. Generally, at least 0.1 mol, preferably 0.2-5.0 mol, more preferably 1.0-2.0 mol, are used per mol of compound (II).

The compound of formula II can also be treated with an oxygen scavenger in the absence of a solvent. In general, however, the operation is carried out in the presence of a solvent, in particular a proton-free solvent. When a Lewis acid or an iodo-trialkylsilane is used as an oxygen scavenger, the solvent used is a halogenated hydrocarbon such as methylene chloride, chloroform, 1,2-difluoroethane, with good results.

When trialkylsilyl perfluoroalkane sulfonate is used as the oxygen scavenger, it is preferable to use acetonitrile or ortho formic acid ester.

Under mild conditions, the reaction proceeds smoothly. The treatment temperature is -40 ° C to 150 ° C, preferably -20 ° C to 100 ° C, preferably -10 ° C to 90 ° C.

Treatment of the compounds of formula (II) with an oxygen scavenger under the above conditions gives the compounds of formula (I). In the case where the oxygen scavenger is a Lewis acid, this and the product may form a complex. In this case, the product may be isolated by adding water; In this way, the complex is decomposed and the target compound can then be isolated in a known manner.

192,451

The compound of formula (II) of the present invention is isolated from the reaction mixture in a known manner, for example by extraction, chromatography, distillation, crystallization.

Of the compounds of formula (II), compounds of formula (I-1) are particularly preferred, wherein Ar ² is a thienyl group; R ¹ 'is hydrogen or lower alkyl; R ³ 'and R ⁴ ' are independently lower alkyl; R ³ 'and R ⁴ ' together may form a lower alkylene group; R ⁵ 'is lower alkyl, lower haloalkyl, d- or 1-10-camphoryl, or a group of formula (1); R ¹ , R ⁶ , R ⁷ and Ar ¹ are as defined above.

In the compounds of the formula II, Ar and R ¹ together with the adjacent carbon atom may form a fused ring. Examples of compounds of formula II containing a ring fused to Ar and R ¹ include compounds of formula II-1 and II-2.

These compounds are hydrolyzed or treated with an oxygen scavenger to give compounds (3) and (4).

The compounds of formula (II) may be prepared starting from the α-halo ketone of formula (V); wherein X is halogen, Ar and R ¹ are as defined above. The reaction is illustrated in Scheme A.

In the reaction scheme, M is an alkali metal, Hal is a halogen atom, preferably chlorine, Ar, R ¹ , R ³ , R ⁴ , R ⁵ and X are as defined above.

The compounds of formula (V) may be prepared by reacting the formula (VIII) with a compound of formula wherein R ¹ and X represents the presence of the compound of the above formula (IX) is subjected to Friedel-Crafts reaction; in formula (IX), Ar is as defined above; alternatively, a compound of formula X wherein Ar and R ¹ are as defined above is halogenated in a manner known per se.

The reaction scheme described below is detailed below.

Step One: (V) - (VI)

In this step, compounds of formula (V) are treated with an alkali metal alkoxide of formula R ³ OM. The reaction is carried out in the presence of the corresponding alcohol R ³ OH; In this way, α-hydroxy ketone acetal of formula (VI) is obtained. In the resulting compound of formula VI, R ⁴ is then R ³ . The alkali metal alkoxide is preferably lithium alkoxide, sodium alkoxide or potassium alkoxide. Due to its favorable price, it is preferable to use sodium alkoxide. Generally, at least 1 mol of alkali metal alkoxide is used per mole of the compound of formula (V). The reaction proceeds faster when the amount of alkoxide is between 1.5 and 3 moles. The amount of alcohol also present is at least 1 mol per liter of the compound of formula (V). It is expedient to take alcohol in excess so that it can also act as a solvent. It is also advantageous to use a proton-free solvent which does not participate in the reaction. The proton-free solvent may be diethyl ether, tetrahydrofuran, I) MF (dimethylformamide) or 1,2-dimethoxyethane. The reaction proceeds smoothly at temperatures between -20 ° C and 120 ° C. To simplify the operation, the reaction is carried out at room temperature to 60 ° C.

Alternatively, this step is carried out by reacting a compound of formula (V) with an alkali metal alkoxide of formula R ³ OM in a proton-free solvent; as a solvent, diethyl ether, tetrahydrofuran or 1,2-dimethoxyethane; In this way, the ethoxy compounds of formula VII are obtained. The resulting compound is treated with an alcohol of the formula R ⁴ OH in the presence of a catalytic amount of an alkali metal alkoxide R ⁴ OM; The alpha-hydroxy ketone acetal derivative of formula VI is thus obtained (see Examples 8 and 9).

This procedure provides a compound of formula VI wherein R ³ and R ⁴ are different.

The reaction of the compound of formula (V) with an alkali metal alkoxide R ³ OM is generally carried out at a temperature between 0 ° C and 60 ° C; from 1 to 3 moles of the alkali metal alkoxide per mole of the compound of formula (V). The reaction of the compound of formula VII with the alcohol of the formula R ⁴ OH is generally carried out at a temperature of 0 ° C to 100 ° C; At least 1 mole of alcohol is used per mole of compound (VII). Preferably, the alcohol is taken in excess and is thus used as a solvent.

Alternatively, the α-halo ketone of formula (V) is reacted in the presence of a divalent alcohol (e.g., ethylene glycol, propylene glycol, or 1,3-propanediol) with a mono-alkali metal salt of the divalent alcohol; In this way, a-hydroxy ketone acetal of formula (VI) is obtained. This process provides a compound of formula VI wherein R ³ and R ⁴ together form an alkylene group such as ethylene, propylene or trimethylene (see Example 111).

This reaction is conducted at a general temperature of 0 ° C to 100 ° C; at least 1 mole, preferably 1.5 to 3 moles, of a divalent alcohol mono-alkali metal salt; 0.5 molar, preferably 2 to 10 mol, of bivalent alcohol are taken. A proton-free solvent which is not involved in the reaction is also added to the reaction mixture. The solvent may be diethyl ether, tetrahydrofuran or 1,2-dimethoxyethane.

Compounds of general formula (VI) obtained in the above reaction, wherein Ar is other than phenyl and 4-chlorophenyl and wherein R ¹ is other than hydrogen, are new compounds are not reported in the literature. 5

Among the compounds of formula VI, the following are mentioned: compounds of formula VI wherein

Ar means 10

4-Prenyl-phenyl-N-methyl-phenothiazinyl-1-methyl-pyrrolyl-2-fluoro-4-biphenylyl-2-acetylamino-4-biphenylyl-

4-Chloro-phenyl-3-chloro-4- (3-pyrrolin-1-yl) -phenylR ¹ is methyl hydrogen or methylhydrogen or methylmethylmethylisopropyl and methylthe second step: (VI) - (II)

This process step is treated with the α-hydroxyketone acetal compound of formula (VI) with an ^R5 -SO2Hal or (R ⁵ SO 2) ₂ O O-sulfonylating agent of the formula 30; In this way, compounds of formula II are obtained.

Among the O-sulfonating agents, 35 are mentioned: benzenesulfonyl chloride, p-toluenesulfonyl chloride, p-bromobenzenesulfonyl chloride, p-nitrobenzenesulfonyl chloride and naphthalenesulfonyl chloride; and alkanesulfonyl halides or alkenesulfonic anhydrides such as methanesulfonyl chloride, butylsulfonyl chloride, methanesulfonic anhydride, trifluoromethanesulfonic anhydride, trifluoromethanesulfonyl chloride, d-10-camphorsulfonyl camphorsulfonyl chloride. 45

The reaction is conveniently conducted under neutral or basic conditions, using 1 mol of tertiary amine such as triethylamine, pyridine or 4-dimethylaminopyridine per mol of compound (VI). Thus, the reaction proceeds at a relatively low temperature, between 0 ° C and room temperature. The operation may also be carried out in the presence of a proton-free solvent which does not participate in the reaction. The solvent may be methylene chloride or diethyl ether.

The starting compound (II) can be prepared in two steps starting from the α-halo ketone (V). This compound can also be prepared by other methods, for example starting from the 1-alkoxy-1-alkene derivative of the formula (XI) in the 1-position. Ar, R ¹ and R ³ are as defined above. This compound is oxidized to give the epoxy compound of formula VII, the epoxy compound is converted to the a-hydroxy ketone acetal compound of formula VI, and the compound of formula VI is converted into the compound of formula II . Alternatively, the corresponding α-sulfonyloxy ketone is converted to the compound of formula II by acetalization. Alternatively, the α-oxo-ketone acetal of formula (XII) wherein Ar, R ¹ , R ³ and R ⁴ are as defined above is reduced; In this way, a compound of formula (VT) is converted to a compound of formula (II).

Thus, the α-sulfonyloxy ketone acetal of formula (II) can be readily prepared in various ways.

The compounds of formula (I) have a beneficial therapeutic effect and are also useful in agriculture. Among these compounds, the following are mentioned:

Ibuprofen, Naproxen and o- [4- (1-oxo-2-isoindolinyl) phenyl] propionic acid (anti-inflammatory agent, Indoprofen). In addition, methyl ester of α- (2-thienyl) propionic acid, α- [4- (tert-butyl) phenyl] isovaleric acid, methyl cis (4-alkoxyphenyl) isovaleric acid, α- (4-biphenylyl) -propionic acid, 1- (4-difluoromethoxyphenyl) -isovaleric acid methyl ester, α- (4-alkoxyphenyl) -propionic acid methyl ester.

These compounds are useful as intermediates in the preparation of anti-inflammatory agents and insecticides.

The following examples illustrate the present invention. The substituents of the compounds of formula II prepared according to the Examples are summarized in Table 1

Table 2

Ά examples Compounds of formula (II) prepared according to the invention The serial number of the example Price Ri R3 R ⁴ R ⁵ 1 phenyl methyl- methyl- methyl- p-methylphenyl 5 p-isobutylphenyl methyl- methyl- methyl- methyl- 8 p-methoxy-phenyl methyl- methyl- methyl- p-fenfl- 10 p-t-butylphenyl isopropyl methyl- methyl- methyl- > 12 phenyl H ethylene p-methylphenyl 13 phenyl H ethylene p-bromophenyl

192,451

Table I (continued)

The serial number of the example

15 2thienyl methyl- 16 p-isobutylphenyl methyl- 17 phenyl methyl- 19 p-methoxyphenyl methyl- 20 2thienyl methyl- 21 2thienyl methyl- 24 p-acetylamino phenyl methyl- 26 p-fluorophenyl methyl- 27 p-fluorophenyl methyl- 29 6-methoxy-2-naphthyl methyl- 30 6-methoxy-2-naphthyl methyl- 32 p-chlorophenyl methyl- 34 p- (l-oxo-2- -izoindolinil) phenyl methyl- 36 biphenyl methyl- 38 1,2,3,4 -tetrahidronaftol- 40 p-difluoromethoxy phenyl methyl- 42 p-difluoromethoxy phenyl isopropyl 44 p-ethoxyphenyl isopropyl 46 p-methoxyphenyl isopropyl 48 p-methoxyphenyl isopropyl 49 6-methoxy-2-naphthyl methyl- 50 6-methoxy-2-naphthyl methyl- 51 6-methoxy-2-naphthyl methyl- Example 1

9.81 g of p-toluenesulfonyl chloride are dissolved in 10 ml of anhydrous pyridine and the mixture is stirred at room temperature. Anhydrous pyridine solution (10 ml) containing 6.65 g of α-hydroxypropiophenone dimethylacetal was added dropwise over 10 minutes. The mixture was then stirred for 48 hours. The reaction mixture was poured into 200 ml of ice water and stirred for 2 hours. The resulting precipitate was filtered, washed, and dried over potassium hydroxide in vacuo. This gives 10.91 g of α- (p-toluenesulfonyloxy) -propiophenone dimethylacetal as colorless crystals.

Yield: 92%.

Mp 62-63 ° C (from ligroin).

IR: 1360, 1190, 1175, 1090, 1060, 1040, 910, 710 cm -1.

MMR (CDCl ₃ ): δ 1.07 (3H, d, J = 6Hz), 2.73 (3H, s), 3.08 (3H, s), 3.15 (3H, s), δ , 95 (1H, q, J = 6Hz), 7.33 (7H, m), 7.77 (2H, d, J = 9Hz).

Analysis for [C18H22O5S] [%]:

Calculated: C, 61.70; H, 6.33; S, 9.15;

Found: C, 61.72; H, 6.26; S, 9.19.

R3 Ra ^R5

methyl- methyl- methyl- methyl- methyl- phenyl ethyl- ethyl- p-methylphenyl methyl- methyl- methyl- methyl- methyl- p-methylphenyl methyl- methyl- phenyl methyl- methyl- methyl- methyl- methyl- methyl- methyl- methyl- p-methylphenyl methyl- methyl- methyl- methyl- methyl- d-10-camphoryl methyl- methyl- p-methylphenyl methyl- methyl- methyl- methyl- methyl- methyl- methyl- methyl- methyl- methyl- methyl- methyl- methyl- methyl- methyl- methyl- methyl- methyl- methyl- methyl- methyl- ethylene methyl- methyl- methyl- 1-10-camphoryl methyl- methyl- p-methylphenyl methyl- methyl- phenyl

Example 2

Sodium methoxide (1.134 g) was dissolved in methanol (20 mL) and stirred at room temperature under argon. To the solution was added 2,692 g of N-bromo-pisobutylpropiophenone in 20 ml of anhydrous methanol at room temperature for 30 minutes. After the addition was complete, water (50 mL) was added and the mixture was extracted with diethyl ether (3 x 20 mL). The extract was washed with water (20 mL) and dried over anhydrous magnesium sulfate and potassium carbonate and concentrated under reduced pressure in the presence of a small amount of potassium 50 carbonate; This gives 2.370 g of a-hydroxy-p-isobutylpropiophenone dimethylacetal as a colorless oily product.

Yield: 94%.

For analysis, the product was purified by column chromatography (Florisil; methylene chloride).

Infrared 3500, 2950, 1460, 1100, 1050, 980, 850, 800, 740 απ ''.

MMR (CDCl 3): δ 0.91 (6H, d, J = 7Hz), 0.96 (3H, d, J = 7Hz), 1.6-2.1 (1H, m), 2, 43 (2H, d, J = 7Hz), 2.57 (1H, broad s), 3.20 (3H, s), 3.30 (3H s), 4.06 (1H, q, J = 7 Hz), 7.08 (2H, d, J = 9Hz), 7.33 (2H, d, J = 9Hz).

192,451

Analysis for C15H24O3 [t%]:

Calculated: C, 71.39; H, 9.59;

Found: C, 71.39; H, 9.48.

Example 3

0.979 g of sodium methoxide is dissolved in 10 ml of anhydrous methanol and the solution is stirred at room temperature under argon. A solution of a-chloro-p-isobutylpropiophenone (2.036 g) in anhydrous methanol (10 mL) was added dropwise over 20 minutes and the mixture was stirred at room temperature for 4 hours. Standard work up of the reaction mixture gave 2.158 g (95% yield) of α-hydroxy-p-isobutylpropiophenone dimethylacetal as a pale yellow oily product.

Example 4

As in Example 1, a- (p-toluenesulfonyloxy) -? - isobutylpropiophenone dimethylacetal was prepared as a colorless crystalline product. The starting material was α-hydroxy-β-isobutylpropiophenone dimethylacetal.

Yield: 89%.

Melting point: 64-65 ° C (from hexane).

IR: 2960, 1360, 1185, 1090, 1050, 930, 915, 780 cm @ -1.

MMR (CDCl ₃ ): δ 0.88 (6H, d, J = 7Hz), 1.09 (3H, d, J = 7Hz), 1.5-2.1 (1H, m), 2.40 (3H, s), 2.42 (2H, d, J = 7Hz), 3.07 (3H, s), 3.15 (3H, s), 4.93 (1H, q, J) = 7Hz), 6.9-7.4 (6H, m), 7.72 (2H, d, J = 9Hz).

Analysis for the formula (C22H30O5S) [t%]:

Calculated: C, 64.99; H, 7.44; S, 7.89%.

Found: C, 64.78; H, 7.26; S, 7.93%.

Example 5

Dissolve 2.94 g of methanesulfonyl chloride in 5 ml of anhydrous pyridine. The solution was stirred under ice-cooling. 3.23 g of a-hydroxy-p-isobutylpropiophenone dimethylacetal in 10 ml of anhydrous pyridine are added to the solution over about 15 minutes. The mixture was stirred under ice-cooling for 1 hour and then at room temperature for 30 minutes. Water (30 ml) was added and the mixture was stirred for 1 hour. The mixture is extracted three times with 10 ml of methylene chloride, the extract is extracted

Wash three times with 10 ml of water and then dry with anhydrous magnesium sulfate. The organic phase is concentrated in the presence of a small amount of anhydrous potassium carbonate. An oily product is obtained which is purified by column chromatography (Florisil; methylene chloride). This gives 3.477 g of? - (methanesulfonyloxy) -? - isobutylpropiophenone dimethylacetal as a colorless oily product.

Yield: 79%.

IR: 2960, 1175, 1095, 1065, 1350, 1040, 915 cm in ^{the first}

MMR (CDCl 3):? 0.88 (6H, d, J = 7Hz), 1.16 (3H, d, J = 7Hz), 1.6-2.1 (1H, m),

2.44 (2H, d, J = 7Hz), 3.06 (3H, s), 3.18 (3H, s), 3.26 (3H, s), 4.95 (1H, q, J = 7Hz), 7.10 (2H, d, J = 8Hz), 7.32 (2H, d, J = 8Hz).

Analysis for formula (6ι ₆ Η ₂₆ Ο ^ 5) [t%]:

Calculated: C, 58.16; H, 7.93; S, 9.69%.

Found: C, 58.06; H, 7.80; S, 9.60%.

Example 6

9.20 g of sodium methoxide are suspended in 10 ml of anhydrous diethyl ether and under argon, and the solution is stirred under ice-cooling. Then, a solution of 15.0 g of α-bromo-p-methoxypropiophenone in 80 ml of anhydrous diethyl ether is added dropwise over 40 minutes. At the end of the addition, the insolubles were removed by filtration under argon. The filtrate was concentrated under reduced pressure to give 7.88 g

1- (4-Methoxyphenyl) -1-methoxy-1,2-epoxy-pr opaate was obtained as a pale yellow oil.

Yield: 68%.

MMR Spectrum (CDCl <): δ 1.00 ≤ 3H, d, J =

Hz), 3.23 (3H, s), 3.52 (1H, q, J = 6Hz), 3.82 (3H, s), 6.92 (2H, d, J = 7Hz), 7 , 38 (2H, d, J = 7Hz).

Example 7 g 1- (4-methoxyphenyl) -1-methoxy-1,2-epoxypropane and 200 mg sodium methoxide in 30 ml of anhydrous methanol were stirred for 15 hours at room temperature. Water (50 mL) was added and the mixture was extracted with diethyl ether (3 x 20 mL). The extract was dried over anhydrous magnesium sulfate and potassium carbonate and concentrated under reduced pressure in the presence of a small amount of anhydrous potassium carbonate. 8.26 g of a-hydroxy-p-methoxypropiophenone dimethylacetal are thus obtained in the form of a colorless oily product. The resulting material was subjected to column chromatography (Fi orisiil; methylene chloride) for analysis.

Yield: 61%.

IR: 3520, 1050 ^cm-first MMR (CDCl 3): δ 0.94 (3H, d, J =)

Hz), 2.35 (1H, d, J = 4Hz), 3.20 (3H, s), 3.33 (3H, s), 3.78 (3H, s), 4.05 (1H, dq, J = 4 and 7Hz), 6.18 (2H, d, J = 9Hz), 7.35 (2H, d, J = 9Hz).

Analysis ai (Ci2H ₁₈ O ₄₎ Calcd [wt%] Calculated: C: 63.70; H, 8.02%.

Found: C, 63.98; H, 8.08%.

Example 8

Dissolve 2.67 g of p-toluenesulfonyl chloride in 5 ml of anhydrous pyridine and stir at room temperature. To the solution was added a solution of about 1.58 g of α-hydroxy-p-methoxy-p 'opiophenone dimethylacetal in 5 ml of anhydrous pyridine over 10 minutes. Else-71

After stirring for 192 hours, ice water (20 g) was extracted with diethyl ether (3 x 20 ml). The extract was washed with water (20 mL), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure in the presence of a small amount of anhydrous potassium carbonate. This gives 2.12 g of α- (p-toluenesulfonyloxy) -p-methoxypropiophenone dimethylacetal as a pale yellow oily product.

Yield: 80%.

IR: 1600, 1510, 1350, 1245, 1170, 1090, 1055, 1035, 905 cm -1.

NMR (CDC1 ₃₎ d 1.07 (3H, d, J =

Hz), 2.40 (3H, s), 3.07 (3H, s), 3.12 (3H, s),

3.75 (3H, s), 4.92 (1H, q, J = 7Hz), 6.7-7.0 (2H, m), 7.1-7.4 (4H, m), 7 , 73 (2H, d, J =

Hz).

Example 9

1.62 g of sodium methoxide are dissolved in 20 ml of anhydrous methanol, and the solution is stirred at room temperature under argon.

A solution of 2.64 g of α-bromo-p-tert-butyl isovalerophenone in 20 ml of anhydrous methanol is added over about 15 minutes to the above solution, and the mixture is stirred at room temperature for 18 hours.

Workup of the reaction mixture as in Example 2 gave 2.44 g of α-hydroxy-β-tert-butyl-isovalerophenone dimethylacetal as a pale yellow oily product.

Yield: 98%.

IR: 2950, 1110, 1040 cm ^-1 .

MMR (CDCl3): d 0.70 (3H, d, J = 7Hz), 0.90 (3H, d, J = 7Hz), 1.32 (9H, s), 1.0-1 , 6 (1H, m), 2.45 (1H, broad s), 3.22, (3H, s), 3.25 (3H, s), 3.67 <1H, d, J = 6Hz) , 7.33 (4H s).

Example 10

Methanesulfonyl chloride (1.90 g) was dissolved in dry pyridine (5 mL) and stirred at room temperature; a solution of 2.34 g of? -hydroxy -? - t -butyl) isovalerophenone dimethylacetal in 5 ml of anhydrous pyridine is added dropwise over 10 minutes. The mixture was stirred at this temperature for a further 24 hours. The mixture was worked up as described in Example 5; 1.63 g of α-methanesulfonyloxy-β-tert-butyl isovalerophenone dimethylacetal are obtained in the form of a colorless oily product (the mixture is left at room temperature and the compound crystallizes).

Yield: 55%.

O. p. Mp _: 80-86 ° C.

IR: 2960, 1357, 1176,

1060, 955 cm ^-1 .

NMR (CDC1 ₃₎ d 0.70 (3H, d, J =

Hz), 0.90 <3H, d, J = 7Hz), 1.32 (9H, s),

1.4-1.9 (1H, m), 3.17 (3H, s), 3.205 (3H, s),

3.26 (3H, s), 4.76 (1H, d, J = 4Hz), 7.37 (4H, ^s)

Analysis (Ci8H ₃₀ Ob) calcd [wt%] Calculated: C: 60.30; H, 8.44; S, 8.95%. Found: C, 60.07; H, 8.23; S, 9.07%.

Example 11

To a mixture of 7.12 g of? -Acetoxyethaneophenone in 7.44 g of ethylene glycol and 0.200 g of p-toluenesulfonic acid monohydrate is added 100 ml of benzene and the mixture is heated under reflux. The resulting water is removed using a Dean-Stark-f cartridge. The mixture was refluxed for 21 hours and ethylene glycol (4.00 g) was added. The mixture was refluxed for a further 6 hours. The resulting water was discarded. After cooling, 30 ml of saturated aqueous sodium bicarbonate solution and 20 ml of water are added and the mixture is extracted twice with 30 ml of diethyl ether. The combined extracts were washed with water (10 mL), dried over magnesium sulfate and concentrated under reduced pressure. 7.874 g of product are obtained. The product was found to be a mixture of c: -acetoxyacetophenone-ethylene-acetal and α-hydroxy-acetophenone-ethylene-acetal based on MMR and gas chromatography. The mixture was dissolved in methanol (20 mL) and potassium carbonate (0.300 g) was added, followed by stirring at room temperature for 4 hours. After addition of 200 ml of water, colorless crystals precipitated and were filtered, dried over potassium hydroxide under vacuum overnight to give 4.79 g of α-hydroxyacetophenone ethylene acetal.

Yield: 67%.

NMR (CDC1 ₃₎ d 2.10 (1Ή, br s), 3.70 (2H, br s), 3.7-4.0 (2H, m), 4,0-

4.2 (2H, m), 7.2-7.6 (5H, m).

Example 12

To 0.900 g of α-hydroxyacetophenone ethylene acetal was added 5 ml of pyridine. After stirring under ice-cooling, 1.08 g of p-toluenesulfonyl chloride was added. The mixture was ice-cooled for 2 hours and then at room temperature for 1 hour. The reaction mixture was again cooled with ice. After addition of 10 ml of water, the mixture was stirred for 1 hour, extracted three times with 20 ml of diethyl ether. The combined extracts were washed with water (10 mL, 10 mL), dried over anhydrous magnesium sulfate to give 1.584 g of crystalline product under reduced pressure. The residue was washed with a small amount of hexane to give 1.330 g of α- (p-toluenesulfomloxy) -acetophenone-ethylene-acetal as colorless crystals.

Yield: 80%.

I NMR (CDC1 ₃₎ d 2.40 (3H, s);

192,451

3.7-3.9 (2H, m), 3.9-4.1 (2H, m), 4.11 (2H, s),

7.1-7.5 (5H, m), 7.55 (2H, d, J = 8Hz).

Example 13

As in Example 12, α- (p-bromobenzenesulfonyloxy) -acetophenone-ethylene-acetal was prepared as colorless crystals. The starting material was α-hydroxyacetophenone ethylene acetal.

Yield: 86%.

MMR (CDCl ₃ ): δ 3.7-3.9 (2H, m), 3.9-4.1 (2H, m), 4.16 <2H, s), 7.2-7, Δ (5H, m), 7.63 (4H, s).

Example 14

0.46 g of metal sodium are dissolved in 10 ml of anhydrous methanol and the solution is stirred at room temperature. The solution was added over 10 minutes

A solution of 2.9 g of 1- (2-thienyl) -2-bromo-1-propanone in 10 ml of anhydrous methanol is added dropwise and the mixture is stirred for an additional 3.5 hours at room temperature. Work up as in Example 3 to give 1.900 g of 1- (2-thienyl) -2-hydroxy-1-propane dimethylacetal as a colorless oily product.

Yield: 94%.

IR: 3450, 1110, 1055,

980, 855, 710 cm ^-1 .

MMR (CDCl3): δ = 1.05 (3H, d, J = 7Hz), 2.54 (1H, broad s), 3.26 (3H, s), 3.30 (3H, s), 4.16 (1H, broad q, J = 7Hz), 6.9-7.2 (2H, m), 7.2-7.4 (1H, m).

Example 25

1- (2-Thienyl) -2-hydroxy-1-propanone dimethylacetal (0.606 g) was dissolved in pyridine (5 mL) and stirred under ice-cooling. After more than 1 minute, methanesulfonyl chloride (0.30 mL) was added and the mixture was stirred under ice-cooling for 5 minutes and then at room temperature for 5 hours. After the addition of 30 ml of water, the mixture was stirred at room temperature for 30 minutes and then extracted three times with 30 ml of diethyl ether. The extract was washed twice with 10 ml of water, dried over anhydrous magnesium sulfate and potassium carbonate, and concentrated under reduced pressure. The residue was purified by column chromatography (Florisil; methylene chloride). 0.788 g of 1- (2-thienyl) -2- (methanesulfonyloxy) -1-propanone dimethylacetal are obtained in the form of a colorless oily product.

Yield: 94%.

IR: 1360, 1180, 1120, 1055, 990, 975, 930, 905, 855, 810, 715, 540, 525 ^cm-first

MMR (CDCl 3): δ 1.27 (3H, d, J = 7Hz), 3.09 (3H, s), 3.27 (6H, s), 5.02 (1H, q, J = 7 Hz), 6.9-7.1 (2H, m), 7.2-7.4 (1H, m).

Analysis for the formula (C 10 H 11 O 5. SO) [t%]:

Calculated: C, 42.8; H, 5.75; S, 22.87.

Found: C, 42.64; H, 5.64; S, 22.90%.

Example 16

Benzenesulfonyl chloride (2.01 g) was dissolved in anhydrous pyridine (10 mL) and the solution was stirred at room temperature. A solution of 1.93 g of α-hydroxy-p-isohutylpropiophenone dimethylacetal in 10 ml of anhydrous pyridine is added dropwise over 15 minutes. The mixture was stirred for 72 hours. Work up as in Example 1 to give 2.62 g of α-benzenesulfonyloxy-β-isobutylpropiophenone dimethylacetal as colorless crystals.

Yield: 88%.

Mp: 79-82 ° C.

IR: 2950, 1362, 1195, 1097, 1043, 990, 921, 813, 594 cm ^-1 .

MMR (CDCl ₃ ): δ 0.86 <6H, d, J = 7Hz), 1.08 (3H, d, J = 7Hz), 1.6-2.1 (1H, m), δ , 41 (2H, d, J = 7Hz), 3.02 (3H, s), 3.10 (3H, s), 4.94 (1H, q, J = 7Hz), 7.04 2H, d, J = 9Hz, 7.19 (2H, d, J = 9Hz), 7.36-7.70 (3H, m), 7.84-8.02 (2H, m).

Example 27

1.91 g of p-toluenesulfonyl chloride is dissolved in 10 ml of anhydrous pyridine and the solution is stirred at room temperature. To the solution

A mixture of α-hydroxypropiophenone diethyl acetal (1.13 g) in dry pyridine (10 mL) was added dropwise over about 10 minutes. The mixture was then stirred for 72 hours. After usual work-up and purification by column chromatography (Florisil; methylene chloride), 1.16 g of α- (p-toluenesulfonyloxypropiophenone diethyl acetate) are obtained in the form of a colorless oily product.

Yield: 85%.

IR: 2980, 1360, 1192, 1178, 1087, 1055, 1042, 920 ^cm-first

MMR (CDCl 3): δ 0.8-1.3 (9H, m), 2.38 (3H, s), 3.1-3.6 (4H, m), 4.89 (1H, q , J = 7Hz), 7.1-7.5 (7H, m), 7.80 (2H, d, J = 9Hz).

Analysis for (C20H26O5S): [t%]:

Calculated: C, 63.46; H, 6.93; S, 8.47%.

Found: C, 63.54; H, 6.90; S, 8.35%.

Example 28

1- (4-Methoxyphenyl) -2-hydroxy-1-propanone dimethylacetal was prepared as in Example 14 in the form of a pale yellow oily product. 1- (4-methoxyphenyl) -2-bromo-1-propanone is used as starting material.

The crude product obtained was used without purification as in Example 19.

Example 29

As in Example 5, 1- (4-methoxyphenyl) -2-methanesulfonyloxy-1-propanone dimethylacetal was prepared as a pale yellow oil. Starting with 1 - <(4-methoxyphenyl) -2-hydroxy-1-propanone-dimethylacetate 91

192,451 (prepared according to Example 18).

Yield: 80.1% [based on 1- (4-methoxyphenyl) -2-bromo-1-propanone].

IR: 2935, 1615, 1517, 1358, 1257, 1176, 1100, 1065, 145, 915 cm ^-1 .

MMR (CDCl ₃ ) δ 1.18 (3H, d, J =)

Hz), 3.09 (3H, s), 3.21 (3H, s), 3.28 (3H, s),

3.80 (3H, s), 4.97 (1H, q, J = 6Hz), 6.87 (2H, d, J = 9Hz), 7.37 (2H, d, J = 9Hz) .

Example 20

As in Example 17, 1- (2-thienyl) -2- (p-toluenesulfonyloxy) -1-propanone dimethylacetal was prepared as a colorless oily product. 1- (2-thienyl) -2-hydroxy-1-propanone dimethylacetal was used as starting material.

Yield: 64%.

IR: 1360, 1190, 1180, 1060, 985, 925, 905, 820, 790, 710, 665, 565 ^cm-first

MMR Spectrum (CDCl ₃ ): δ 1.19 (3H, d, J

Hz), 2.40 (3H, s), 3.08 (3H, s), 3.14 (3H, s), 4.98 (1H, q, J = 7Hz), 6.94 (2H, d, J = 3 Hz),

7.2-7.4 (3H, m), 7.80 (2Ή, d, J = 8Hz).

Example 21

In the same manner as in Example 17, 1- (2-thienyl) -2- (benzenesulfonyloxy) -1-propanone dimethylacetal was prepared as a colorless oily product. Yield: 83%. 1- (2-thienyl) -2-hydroxy-1-propanone dimethylacetal was used as starting material.

IR: 1360, 1190, 1060, 980, 925, 900, 590, 555 ^cm-first

MMR (CDCl ₃ ): δ 1.20 (3H, d, J = 7Hz), 3.08 (3H, s), 3.14 (3H, s), 5.01 (1H, q, J = 7 Hz), 6.8-7.1 (2H, m), 7.2-7.4 (1H, m),

7.4-7.7 (3H, m), 7.9-8.1 (2H, m).

Example 22

1.30 g (56.5 mmol) of metal sodium are dissolved in 30 ml of anhydrous ethanol and the mixture is stirred at room temperature. A solution of 5.33 g (0.025 mol) of α-bromopropiophenone in 20 ml of anhydrous ethanol is added dropwise over 15 minutes. The mixture was stirred at room temperature for 40 minutes. Water (100 mL) was added and the mixture was extracted with diethyl ether (2 x 60 mL). The combined extracts were washed with water, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure. The residue was dissolved in ethanol containing 30 ml of catalytic metal sodium, and the solution was stirred at room temperature for 2 days. Workup as described in Example 2 gave 4.497 g of 1-phenyl-2-hydroxy-1-propanone diethyl acetal as a colorless oily product.

Yield: 80.2%.

IR: 2960, 1452, 1120, 1092, 1057, 1040, 772, 709 ^cm-first

MMR (CDCl ₃ ) δ δ 0.94 (3H, d, J =)

Hz), 1.05-1.40 (6H, m), 2.61 (1H, broad s), 3.22-3.83 (4H, m), 4.05 (1H, q, J = 6 Hz);

7.1-7.7 (5 H, m).

Example 23

As in Example 14, 1- (4-acetylaminophenyl) -2-hydroxy-1-propanone dimethylacetal was prepared as a glass product. Starting material is 1 - '(4-acetylaminophenyl) -2-chloro-1-propanone. Without purification, the crude product was used as in Example 24.

NMR (CDC1 _3): δ 0.95 (3H, d, J =

Hz), 2.14 (3H, s), 2.94 (1H, broad s), 3.21 (3H, s), 3.33 (3H, s), 4.10 (1H, q, J = 7 Hz),

7.37 (2H, d, J = 8Hz), 7.51 (2H, d, J = 8Hz),

8.93 (1H, broad s).

Example 24

The 1- (4-acetylaminophenyl) -2-hydroxy-1-propanone dimethylacetal obtained in Example 23 was dissolved in pyridine (5 ml) and methanesulfonyl chloride (0.60 ml, 0.89 g) was added. . The mixture was stirred at room temperature for 5 hours. The reaction mixture was cooled with ice and water (30 mL) was added. The temperature was then allowed to warm to room temperature, and the mixture was stirred for 10 minutes and then extracted with ethyl acetate (4 x 20 mL). The combined extracts were dried by addition of anhydrous sodium sulfate followed by anhydrous magnesium sulfate, and the organic solution was concentrated under reduced pressure. The residue was purified by column chromatography (Florisil; methylene chloride and diethyl ether); This gives 1.537 g of 1- (4-acetylaminophenyl) -2-methanesulfonyloxy-1-propanone dimethylacetal as a colorless glassy product. Yield: 93%. Calculated for 1- (4-acetylaminophenyl) -2-chloro-1-propanone.

Infrared 1675, 1610, 1540, 1350, 1175, 915, 525 cm ^-1 .

NMR (CDC1 _3): δ 1.14 (3H, d), 2.52 (3H, s), 3.08 (3H, s), 3.18 (3H, s), 3.24 (3H, s);

4.94 (1H, q, J = 7Hz), 7.36 (2H, d, J = 9Hz),

7.54 (2H, d, J = 9Hz), 8.52 (1H, broad s).

Example 25

1- (4-Fluorophenyl) -2-hydroxy-1-propanone dimethylacetal was prepared as in Example 14 as a pale yellow oily product. 1- (4-Fluorophenyl) -2-bromo-1-propanone was used as starting material. The product obtained can be used without further purification as in Examples 22 and 27.

IR: 2975, 2937, 1610,

1512, 1230, 1159, 1105, 1053, 982, 839 cm ^-1 . MMA spectrum (CDCl ₃ ): δ 0.93 (3H, d, J =

Hz), 2.53 (1, broad s), 3.23 (3H, s), 3.33 (3H,

-101

192,451

s), 4.08 (1H, broad q, J = 6Hz), 6.83-7.18 (2H, m), 7.32-7.60 (2H, m).

Example 26

As in Example 5, 1- (4-fluorophenyl) -2-methanesulfonyloxy-1-propanone dimethylacetal was prepared as a colorless oily product. 1- (4-Chlorophenyl) -2-hydroxy-1-propanone dimethylacetal prepared according to Example 25 was used as starting material. Yield: 82.3% based on 1- (4-fluorophenyl) -2-bromo-1-propanone.

IR: 2940, 1610, 1512,

1359, 1228, 1180, 1160, 1098, 1067, 1045, 972, 918 ^cm-first

MMR (CDCl ₃ ): δ 1.15 (3H, d, J = 6Hz), 3.06 (3H, s), 3.21 (3H, s), 3.24 (3H, s),

4.96 (1H, q, J = 6Hz), 6.88-7.16 (2H, m), 7.32-7.58 (2H, m).

Example 27

In the same manner as in Example 17, l (4-fluorophenyl) -2- (p-toluenesulfonyloxy) -1-propanone dimethylacetal was prepared as crystals. Mp .: 96-99 ° C. 1- (4-Fluorophenyl) -2-hydroxypropanone dimethyl acetal prepared in Example 25 was used as starting material. Yield: 76.2% based on 1- (4-fluorophenyl) -2-bromo-1-propanone.

Melting point: 101 DEG C. (from methanol).

IR: 2948, 1605, 1510,

1360, 1346, 1192, 1181, 1090, 1053, 932, 918, 820, 768, 670, 561 ^cm-first

MMR (CDCl ₃ ): δ 1.05 (3H, d, J =)

Hz), 2.40 (3H, s), 3.08 (3H, s), 3.10 (3H, s),

4.93 (1H, q, J = 6Hz), 6.82-7.08 (2H, m), 7.16-7.46 (4-H, m), 7.73 <2H, d, J = 8 Hz).

Analysis for the formula (C ₁₈ H ₂ iFO ₃ S) [t%]:

Calculated: C, 58.68; H, 5.75%.

Found: C, 58.98; H, 5.96%.

Example 28

As in Example 2, 1- (6-methoxy-2-naphthyl) -2-hydroxy-1-propanone dimethylacetal was prepared as a colorless oily product. 1- (6-methoxy-2-naphthyl) -2-bromo-1-propanone was used as starting material. Yield: 100%. After purification by column chromatography and standing at room temperature, the product crystallizes. (Florisil, methylene chloride). Colorless crystals are obtained.

M.p .: 56-59 ° C.

Infrared 3500, 1637, 1610, 1488, 1276, 1215, 1175, 1118, 1106, 1040, 859 cm ^-1 .

MMR (CDCl ₃ ) δ δ 0.97 (3H, d, J =)

Hz), 2.48 (1H, broad s), 3.20 (3H, 2), 3.36 (3H, s), 3.82 (3H, s), 4.14 (1H, q, J = 7 Hz), 7.00-7.24 (2H, m), 7.40-7.98 (4H, m).

Analysis for the formula [C ₁₆ H ₂₀ O ₄ ] [%]:

Calculated: C, 69.54; H, 7.30%.

Found: C, 69.25; H, 7.28%.

Example 29

As in Example 5, 1- (6-methoxy-2-naphthyl) -2-methanesulfonyloxy-1-propanone-d-methylacetal was prepared as a colorless oily product. As starting material

1- (6-methoxy-2-naphthyl) -2-hydroxy-1-propanone-d-methylacetal was used. Yield: 84%.

IR: 1640, 1615, 1492, 1360, 1280, 1), 182, 901, 820 ^cm-first

NMR (ODC1 _3): <5 1.19 (3H, d, J = 7Hz), 3.09 {3H, s), 3.22 <3H, s), 3.31 (3H, s); 3.87 (3H, s), 5.05 (1H, q, J = 7Hz), 7.04-7.24 (2H, m), 7.42-7.94 (4H, m).

Analysis for [C ₁₇ H ₂₂ O ₆ S] [%]:

Calculated: C, 57.61; H, 6.26; S, 9.05%.

Found: C, 57.21; H, 6.02; S, 8 (85%).

EXAMPLE 30 350 mg of sodium metal are dissolved in anhydrous methanol and the solution is stirred at room temperature. For this solution

After stirring for 24 hours, 2.93 g of 1- (6-methoxy-2-naphthyl) -2-bromo-1-propanone was added. Water (50 mL) was added and the mixture was extracted with methylene chloride (4 x 15 mL). The combined extracts were dried over anhydrous magnesium sulfate followed by anhydrous potassium carbonate and then concentrated under reduced pressure. Yield: 2.845 g of crude 1- (6-methoxy-2-naphthyl) -2-hydroxy-1-propanone dimethylacetal. The crude product (1.11) was dissolved in anhydrous pyridine (3 mL) and stirred at room temperature. To the solution was added 993 mg of d-10-camphorsulfonyl chloride and the mixture was stirred for 40 minutes. After addition of 20 ml of water, the mixture was extracted three times with 10 ml of methylene chloride. The combined extracts were dried over anhydrous magnesium sulfate followed by anhydrous potassium carbonate. The organic phase was concentrated under reduced pressure and the residual oil was purified by column chromatography (Florisil, methylene chloride). 1.467 g of 1- (6-methoxy-2-naphthyl) -2- (d-10-camphorsulfonyloxy) -1-propanone dimethylacetal are obtained in the form of a colorless glass. Yield: 76.8%. [Calculated for 1- (6-methoxy-2-naphthyl) -2-bromo-1-propanone.] The product was composed of a 1: 1 mixture of diastereomers, as determined by MMR and liquid chromatography.

1.067 g of this material was dissolved in 4 ml of methanol and the solution was stirred for 2 days

Stand at 2-4 ° C, allow. 355 mg of colorless crystals are obtained. O.p .:

908.5 ° C. The crystals were recrystallized from methanol to give 220 mg of diastereomer as a pure product. Mp: 102-105 ° C.

[.alpha.] D @ ²⁵ = -32.5 DEG (c = 1, chloroform).

IR: 2950, 1753, 1634, 1611, 1487, 1354, 1273, 1219, 1180, 1166, 1068, 1042, 990, 919, 899, 862, 840 ^cm-first

MMR (CDCl ₃ ): δ 0.87 (3H, s), 1.12 (3H, s), 1.23 (3H, d, J = 6Hz), 1.3-2.7 (7H,

-111

192,451

m), 3.04 ι (1Η, d, J = 15 Hz), 3.24 (3H, s), 3.35 (3H, s), 3.86 (3H, s), 3.86 <1H , d, J = 15 Hz),

5.15 (1H, q, J = 6Hz), 7.04-7.26 (2H, m), 7.46-7.98 (4H, m).

Analysis for (C26 H ₃₃ O ₇ S) Calcd [wt%]:

Calculated: C, 63.78; H, 6.79; S, 6.55%.

Found: C, 63.66; H, 7.06; S, 6.57%.

The other diastereomer can be isolated by liquid chromatography as a colorless oil (column: Microprorasil, Waters Co., column size:

7.8mm X 30mm; solvent: hexane: ethyl acetate 9: 1).

[α] D ²⁵ + 4.2 ° (c = 0.143, chloroform).

IR: 2950, 1750, 1631, 1608, 1485, 1352, 1271, 1216, 1172, 1062, 1040, 985, 914, 895, 855, 810 cm ^-1 .

MMR (CDCl ₃ ): δ 0.91 (3H, s), 1.14 (3 (, s), 1.26 (3H, d, J = 6Hz), 1.3-2.7 (7H) , m), 3.29 (1H, d, J = 5Hz), 3.30 (3H, s), 3.42 (3H, s), 3.74 (1H, d, J = 15Hz), 3.96 <3H, s),

5.20 (1H, q, J = 6Hz), 7.10-7.30 (2H, m), 7.50-8.02 (4H, m).

Example 32

1- (4-Chlorophenyl) -2-hydroxy-1-propanone dimethylacetal was prepared as in Example 17 in the form of a colorless oily product; starting material is 1- (4-chlorophenyl) -2-bromo-1-propanone. This product was used for Example 83 without further purification.

IR: 3450, 2975, 2930, 1600, 1492, 1398, 1108, 1095, 1052, 1016, 980, 829, 743 ^cm-first

Example 32

In the same manner as in Example 17, 1- (4-chlorophenyl) -2- (p-toluenesulfonyloxy) -1-propanone dimethylacetal was prepared as white crystals. Mp .: 76-77 ° C; starting from the (4'-chlorophenyl) -2-hydroxy-1-propanone dimethylacetal prepared as in Example 31. Yield: 86% based on 1- (4-chlorophenyl) -2-bromo-1-propanone.

Melting point: 78-78 ° C (from methanol).

IR: 2945, 1601, 1493, 1364, 1347, 1195, 1188, 1094, 1057, 1110, 936, 919, 822, 789, 669, 565 ^cm-first

NMR (CDC1 _3): <5 1.05 (3H, d, J = 6Hz), 2.40 (3H, s), 3.08 (3H, s), 3.10 (3H, s);

4.93 (1H, q, J = 6Hz), 7.25 (4H, s), 7.27 (2H, d, J = 8Hz), 7.76 (2H, d, J = 8Hz) .

Analysis for the formula (C ₁₈ H ₂ ISO ₃ Cl) [t%]:

Calculated: C, 56.17; H, 5.50; Cl, 9.21; S, 8.33%.

Found: H, 56.22; H, 5.48; Cl: 9.13; S, 8.32%.

Example 33

1- [4- (1-Oxo-2-isoindolinyl) phenyl] -2-hydroxy-1-propanone dimethylacetal was prepared as described in Example 14; starting with 1- [4- (1-oxo-2-isoindolinyl) phenyl] -2-chloro-1-propanone. Yield: 83%. Colorless crystals, m.p. 130-135 ° C.

IR: 3530, 1680, 1515, 1385, 1310, 1120, 1045, 740 ^cm-first

NMR (CDC1 _3): δ 0.96 (3H, d, J = 7Hz), 2.36 (1H, br s), 3.20 (3H, s), 3.33 (3H, s); 4.10 (1H, broad q, J = 7Hz), 4.80 (2H, s),

7.4-7.6 (5H, m), 7.8-8.0 (3H, m).

Analysis for the formula (C19H21NO4) [%]:

Calculated: C, 69.70; H, 6.47; N, 4.28%.

Found: C, 69.63; H, 6.49; N, 4.21%.

Example 34

In the same manner as in Example 24, 1- [4- (1-oxo-2-isoindolinyl) phenyl] -2-methanesulfonyloxy-1-propanone dimethylacetal was prepared as colorless crystals. Starting from 1 [441-oxo-2-isoindolinyl] phenyl] -2-hydroxy-1-propanone dimethylacetal; yield: 95%.

IR: 1695, 1520, 1390, 1350, 1340, 1175, 975, 910, 740 ^cm-first

NMR (CDC1 _3): δ 1.20 (3H, d, J = 7Hz), 3.11 (3H, s), 3.24 (3H, s), 3.30 (3H, s);

4.81 (2H, s), 5.00 (1H, q, J = 7Hz), 7.4-7.6 (5H, m), 7.8-8.0 (3H, m).

Example 35

In the same manner as in Example 14, 1- (4-biphenyl) -2-hydroxy-1-propanone dimethylacetal was prepared as colorless crystals. 1- (4-biphenyl) -2-bromo-1-propanone is used as starting material; She. mp 78.5-80.0 ° C (from a mixture of ether and n-hexane). Yield: 95%.

MMR Spectrum (CI ₁ C ₃ ): δ 1.00 (3H, d, J = 7Hz), 2.44 (1H, d, J = 3.1Hz), 3.23 (3H, s) .

3.37 (3H, s), 4.14 (1H, q, d, J = 7Hz), 7.2-

7.7 and 7.55 (m and s, 9H).

IR: 1118, 1102, 1045, 1007, 979, 838, 770, 735, 695 cm ^-1 .

Analysis for the formula (0 ₁₇ Η ₂ ο0 ₃ ) [t%]:

Calculated: C, 74.97; H, 7.40%.

Found: C, 74.88; H, 7.27%.

Example 36

As described in Example 5, 1- (4-biphenyl) -2-methanesulfonyloxy-1-propane-on-dimethylacetal was prepared as a colorless oily product. 1- (4-Biphenyl) -2-hydroxy-1-propanone dimethylacetal was used as starting material. The product was used without purification.

IR: 1490, 1357, 1335, 1177, 1123, 1100, 1065, 1045, 971, 916, 847, 811, 773, 753, 740, 702, 538, 527 ^cm-first

MMR Spectrum (Cl) Cl ₃ ): 1.21 (3H, d, J = 7Hz), 3.03 (3H, s), 3.24 (3H, s), 3.31 (3H, s) , 5.01 (1H, q, J = 7Hz), 7.1-7.7 (m) - 7.56 (s) full 9H.

-121

192,451

Example 37

1,1-Dimethoxy-2-hydroxy-1,2,3,4-tetrahydronaphthalene was prepared as described in Example 14. The starting material was 2-bromo-1-oxo-1,2,3,4-tetrahydronaphthalene. The material was used without further purification as in Example 38.

IR: 1138, 1080, 1058, 767 cm @ -1.

Example 38

As described in Example 14, 1,1-dimethoxy-2-methanesulfonyloxy-1,2,3,4-tetrahydronaphthalene is obtained in the form of colorless crystals; She. mp: 113-114.5 ° C. 1,1-Dimethoxy-2-hydroxy-1,2,3,4-tetrahydronaphthalene prepared in Example 37 was used as starting material. Yield: 46.5% (based on 2-bromo-1-oxo-1,2,3,4-tetrahydronaphthalene).

M.p. 113-114.5 ° C (recrystallized from methylene chloride / diethyl ether / n-hexane).

IR: 1361, 1340, 1206, 1175, 1141, 1033, 1060, 1050, 981, 959, 949, 917, 847, 781, 768, 625, 546, 530, 510 cm ^-1 .

MMR (CDCl ₃ ): δ 2.37 (2H, m), 2.9 (2H, m), 2.94 <3H, s), 2.98 (3H, s), 3.43 (3H, s);

5.27 (1H, t, J = 3Hz), 7.17 (3H, m), 7.63 (1H, m).

Analysis calculated for (CjaHisOsS) [t%]:

Calculated: C, 54.53; H, 6.34; S, 11.20%.

Found: C, 54.73; H, 6.36; S, 11.10%.

Example 39

In the same manner as in Example 14, 1- (4-difluoromethoxy-phenyl) -2-hydroxy-1-propanone-dimethylacetal was prepared as a colorless oily product. Starting material is 2-bromo-1- (4- (difluoromethoxy) phenyl) propanone.

IR: 3600, 3200, 1515, 1385, 1230, 1130, 1050, 840 cm @ ^-1 .

MMR Spectrum (CDCl 3): δ 3.95 (3H, d, J = 7Hz), 2.37 (1H, d, J = 3Hz), 3.23 (3H, s), 3.33 ( 3H, s), 4.10 (1H, dq, J = 3 and 7Hz), 6.52 (1H, t, J = 74Hz), 7.10 (2H, d, J = 9Hz), 7 , 49 (2H, d, J = 9Hz).

Example 40

In the same manner as in Example 5, 1- (4-difluoromethoxy-phenyl) -2-methanesulfonyloxy-1-propanone-dimethylacetal was prepared as a colorless oily product; starting from 1 - ((4-difluoromethoxy-phenyl) -2-hydroxy-1-propanone dimethylacetal) prepared in Example 39. Yield: 55% [starting from 1- (4-difluoromethoxy-phenyl) -1-propanone].

IR: 1515, 1360, 1235,

1180, 1130, 1100, 1070, 1045, 975, 920, 540, 530 cm ^-1 .

MMR (CDCl ₃ ): δ 1.18 (3H, d, J = 7Hz), 3.09 <3H, s), 3.15 (3H, s), 3.18 (3H, _s ), δ , 98 (1H, q, J = 7Hz), 6.53 (1H, t, J = 74Hz),

7.10 (2H, d, J = 9Hz), 7.45 (2H, d, J = 9Hz).

Example 41

Following the procedure of Example 14, 1- (4- (difluoromethoxy) phenyl) -2-hydroxy-3-methyl-1-butanone-dimethylacetal can be obtained in the form of a colorless oily product; starting from 2-bromo-1- (4-difluoromethoxy-phenyl) -3-methyl-1-butanone.

IR: 3600-3300, 1515, 1390, 1230, 1130, 1050 cm @ ^-1 .

MMR spectrum (CDCl3); &Lt; 5 0.69 (3H, d, J = 6Hz), 0.88 (3H, d, J = 6Hz), 1.2-1.7 (1H, m),

2.50 (1H, d, J = 3Hz), 3.22 (3H, s), 3.24 <3H, s), 3.70 (1H, dq, J = 3 and 6Hz), 6, 50 (1H, t, J = 74Hz), 7.07 (2H, d, J = 9Hz), 7.52 (2H, d, J = 9Hz).

Example 42

In the same manner as in Example 10, 1- (4-difluoromethoxy-phenyl) -2-methanesulfonyloxy-3-methyl-1-butanone-dimethylacetal can be obtained as a colorless oily product. Starting material is 1- (4-difluoromethoxy-phenyl) -2-hydroxy-3-methyl-1-butanone-dimethylacetal. Yield: 76% [1- (4-difluoromethoxy-phenyl) -3-methyl-1-butanone]. The product is crystallized leaving the product at low temperature. O. p. Mp: 60-61 ° C.

IR: 1515, 1350, 1230, 1180, 1145, 1080, 1055, 1035, 975 ^cm-first

MMR (CDCl ₃ ): δ 0.67 (3H, d, J = 6Hz), 0.91 (3H, d, J = 6Hz), 1.4-1.9 (1H, m), δ , 17 <3H, s), 3.19 (3H, s), 3.22 (3H, s), 4.75 (1H, d, J = 4Hz), 6.50 (1H, t, J = 74Hz), 7.08 (2H, d, J = 9Hz), 7.50 (2H, d, J = 9Hz).

Example 43

Dissolve 230 mg of metal sodium in 3 ml of anhydrous methanol. To the solution was added a solution of 1.43 g of 2-bromo-144-ethoxyphenyl) - t -methyl-1-butanone in 2 ml of anhydrous methanol. The mixture was stirred at room temperature for 1.5 hours and then at 50 ° C for 45 minutes. Workup in the usual manner gave crude 1- (4-ethoxyphenyl) -2-hydroxy-3-methyl-1-butanone dimethylacetal (1.344 g) as a colorless product. The product can be used for Example 44 without further purification.

IR: 3600-3300, 1610, 1515, 1485, 1400, 1250, 1175, 1115, 1050, 990, 925, 840, 810 cm ^-1 .

NMR (CDC1 _3): <5 0.68 (3H, t, J = 6Hz), 0.87 (3H, d, J = 6Hz), 1.39 (3H, t, J = 7Hz) , 1.2-1.7 (1H, m),

2.50 (1H, d, J = 3Hz), 3.22 (3H, s), 3.24 (3H,

-131

192,451

s), 3.68 (1H, dd, J = 3 and 5 Hz), 4.01 (2H, q, J = 7 Hz), 6.82 (2H, d, J = 9 Hz), 7.37 (2H, d, J = 9Hz).

Example 44

As described in Example 10, 1- (4-ethoxyphenyl) -2-methanesulfonyloxy-3-methyl-1-butanone-dimethylacetal can be obtained in the form of colorless crystals. 1- (4-Ethoxyphenyl) -2-hydroxy-3-methyl-1-butanone dimethylacetal was used as starting material. Yield: 62% [based on 2-bromo-1- (4-ethoxyphenyl) -3-methyl-1-butanone].

M.p .: 83-87 ° C.

IR: 1610, 1335, 1260, 1245, 1175, 955, 850, 840 cm -1.

MMR (CDCl ₃ ) δ δ 0.71 (3H, d, J =)

Hz), 0.94 (3.H, d, J = 6Hz), 1.40 (3H, t, J =

Hz), 1.5-1.9 (1H, m), 3.18 (3H, s), 3.20 <3H, s), 3.24 (3H, s), 4.02 (2H, q) , J = 7Hz), 4.57 (1H, d, J = 3Hz), 6.85 (2H, d, J = 9Hz), 7.37 (2H, d, J = 9Hz).

Example 45

2.58 g of 1- (4-methoxyphenyl) -2-hydroxy-3-methyl-1-butanone dimethylacetal are obtained in the form of a colorless oil. As starting material

^J 2.71 g of 2- bromo-l- (4-methoxyphenyl) -3-methyl-l-butanone was used; the resulting material was used without further purification in Example 46.

IR: 3600-3300, 1615, 1515, 1255, 1175, 1115, 1045, 840 cm ^-1 .

NMR (CDC1 _3): δ 0.70 (3H, d, J = 6Hz), 0.87 (3H, d, J = 6Hz), 1.2-1.7 (1H, m), 2 , 53 (1H, bs), 3.33 (3H, s), 3.34 (3H, s), 3.69 (1H, d, J = 5Hz), 3.78 (3H, s), 6.83 (2H, d, J = 9Hz), 7.40 (2H, d, J = 9Hz).

Example 46

The 1- (4-methoxyphenyl) -2-hydroxy-3-methyl-1-butanone dimethylacetal (2.58 g) obtained in Example 45 was dissolved in 5 ml of anhydrous pyridine and the solution was stirred under ice-cooling. Methanesulfonic anhydride (2.00 g) was added and the mixture was stirred under ice-cooling for 4 hours and then at room temperature for 2 hours. Water (20 ml) was added; the mixture was stirred at room temperature for 1 hour and then extracted with diethyl ether (3 x 20 mL). The combined extracts were washed twice with 5 ml of water, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The oily product was purified by column chromatography (Florisil, methylene chloride); this way

3.10 g of 1- (4-methoxyphenyl) -2-methanesulfonyloxy-3-methyl-1-butanone dimethylacetal are obtained in the form of a colorless oily product. Leaving the resulting material at room temperature crystallizes. Yield:

93% [based on 2-bromo-1- (4-methoxyphenyl) -3-methyl-1-butanone].

Mp: 71.5-73 ° C.

Infrared 1620, 1525, 1355, 1260, 1180, 1105, 1055, 980, 970, 960, 945, 865, 850 cm ^-1 .

NMR (CDC1 _3): δ 0.69 (3H, d, J = 6Hz), 0.89 (3H, d, J = 6Hz), 1.5-1.9 (1H, m);

3.14 (3H, s), 3.16 (3H, s), 3.21 (3H, s), 3.76 (3H, s), 4.72 (1H, d, J = 4Hz), 6.82 (2H, d, J = 9Hz), 7.36 (2H, d, J = -9Hz).

Example 47

To a suspension of 0.65 g of sodium hydride (55% in mineral oil) in 10 ml of anhydrous tetrahydrofuran is added 2.7 ml of ethylene glycol under ice-cooling. After stirring at room temperature for 40 minutes, 2.71 g

2-Bromo-1- (4-methoxyphenyl) -3-methyl-1-butanone was added and stirring continued at 60 ° C for 12 hours. After adding 50 ml of water, the reaction mixture was extracted three times with 30 ml of methylene chloride. The combined extracts were washed with water (10 mL), dried over magnesium sulfate, and concentrated in vacuo. The oily residue was purified by column chromatography (Florisil, methylene chloride). 719 mg of 2-hydroxy-1- (4-methoxyphenyl) -3-methyl-1-butanone-ethylene-acetal are thus obtained in the form of a colorless oily product. Yield: 29%.

IR: 3600-3400, 1620, 1520, 1255, 1175, 1040, 845 cm -1.

NMR (CDC1 _3): δ 0.88 (3H, d, J =

Hz), 0.90 (3H, d, J = 6Hz), 1.2-1.7 (1H, m), 2.55 (1H, broad d, J = 5Hz), 3.5-4 , 2 (5H, m), 3.77 (3H, s), 6.83 (2H, d, J = 9Hz),

7.36 (2H, d, 9Hz).

Example 48

In the same manner as in Example 10, 1- (4-methoxyphenyl) -2-methanesulfonyloxy-3-methyl-1-butanone ethylene acetal was prepared as colorless crystals. As starting material

2-Hydroxy-1- (4-methoxyphenyl) -3-methyl-1-butanone ethylene acetal was used. Yield: 78%

Mp: 82-83 ° C.

IR: 1610, 1510, 1335, 1250, 1170, 1050, 970, 940, 930, 815 cm ^-1 .

NMR (CDC1 _3): δ 0.91 (6H, d, J =

Hz), 1.5-1.9 (1H, m), 2.99 (3H, s), 3.6-4.2 (4H, m), 3.75 (3H, s). 4.67 (1H, d, J = 4Hz), 6.83 (2H, d, J = 9Hz), 7.34 (2H, d, J = 9Hz).

Example 49

In the same manner as in Example 30, 1- (6-methoxy-2-naphthyl) was reacted with 1- (6-methoxy-2-naphthyl) -2-hydroxy-1-propanone dimethylacetal and 1-10-camphorsulfonyl chloride. -2- (l-10-camphorsulfonyloxy) -1-propanone dimethylacetal was prepared as a mixture of two diastereomers. This one

-141

Recrystallization from 192,451 twice from methanol twice gave one of the diastereomers as colorless crystals, m.p. 93-96 ° C, [α] D ²³ -32.2 ° (c = 0.801, chloroform). The IR and MMR spectra of this product were identical to those of the 1-> (6-methoxy-2-naphthyl) -2- (d-10-camphorsulfonyloxy) -1-propanone-dimethyl-aoethal diastereomer prepared according to Example 30. one of them having a [α] D ²⁵ + 32.5 ° (c = 1, chloroform).

The 1-10-camphorsulfonyl chloride used as starting material was prepared from the commercially available 1-10-camphorsulfonic acid ammonium salt [[α] D ²² -18.4 ° (c = 5.3, water)]. chloride as described by H. Sutherland and RL Shriner, J. Am. Chem. Soc. 58, 62 (1936), [α] D ²⁶ -32.3 ° (c = 1.36, chloroform). m.p. 58-64 ° C.

Example 50

To a solution of 1- (6-methoxy-2-naphthyl) -2-hydroxy-1-propanone-dimethylacetal (799 mg) and anhydrous pyridine (3 mL) was added p-toluenesulfonyl chloride (833 mg) at room temperature and the mixture was stirred at room temperature. For 3 days. Water (30 ml) was added and the mixture was extracted three times with 10 ml of dichloromethane each. The extracts were combined, dried over anhydrous magnesium sulfate, and concentrated in vacuo. The oily residue was chromatographed on a silica gel column eluting with dichloromethane. There was thus obtained 1- (6-methoxy-2-naphthyl) -2- (p-toluenesulfonyloxy) -1-propanone dimethylacetal as a colorless oil (1.019 g, 81.9%).

IR (neat): 1612, 1489, 1360, 1278, 1192, 1178, 899, 560 ^cm-first

MMR (CDCl3, δ ppm): 1.13 (3H, d, J = 7Hz), 2.40 (3H, s), 3.13 (3H, s), 3.21 (3H, s) , 3.88 (3H, s), 5.04 (1H, q, J = 7Hz), 7.0-

7.9 (10 H, m).

(The letters mean s = singlet; d = doublet; q = quadruplet; m = multiplet.)

Example 51

To a solution of 132 mg of metal sodium and 5 ml of anhydrous methanol was added 879 mg of 1- (6-methoxy-2-naphthyl) -2-bromo-1-propanone and the solution was stirred at room temperature for 7 hours. Water (20 mL) was added and the mixture was extracted three times (10 mL each with dichloromethane). The extracts were combined, 2 drops of pyridine were added and dried over anhydrous magnesium sulfate and evaporated in vacuo. The crude 1- (6-methoxy-2-naphthyl) -2-hydroxy-1-propanone dimethylacetal thus obtained was dissolved without purification in 2 ml of anhydrous pyridine, to this solution with stirring at room temperature, with 0.60 ml of benzenesulfonyl. chloride was added and the mixture was stirred for 20 hours. Water (10 mL) was added and the mixture was extracted three times (10 mL each with dichloromethane). The extracts were combined, washed with water (10 mL), and the organic layer was dried over anhydrous magnesium sulfate and concentrated in vacuo. The oily residue was chromatographed on a silica gel column eluting with dichloromethane. 1.24 g (82.0% of starting material of 1- (6-methoxy-2-naphthyl) -2-bromo-1-propanone) are obtained with a yield of 1- (6-methoxy-2-naphthyl) -2 - (benzenesulfonyloxy) -1-propanone dimethylacetal as a colorless oil.

IR (neat): 1637, 1612, 1488, 1456, 1365, 1278, 1190, 925, 900, 761, 598 ^cm-first

NMR Spectrum (CDC1 _3, <5 ppm): 1.15 (3H, d, J = 7Hz), 3.10 (3H, s), 3.18 (3H, s), 5.08 (1H, q , J = 7Hz), 7.0-8.1 (11H, m).

Claims (3)

PATENT CLAIMS A process for the preparation of a-sulfonyloxy-ketone acetal derivatives having the following general formula (II): - Ar is phenyl optionally substituted with chloro or fluoro, C 1-4 alkyl, phenyl, acetamido, C 1-4 alkoxy optionally substituted with 2 halogens, or 1-oxo-2-isoindolinyl, and 2-thienyl or 6-methoxy-2-naphthyl; - R ¹ is hydrogen or C 1-4 alkyl; or - Ar and R ¹ together are 1,2,3,4-tetrahydronaphthyl; - R ³ and R ⁴ are each independently C 1 -C 4 alkyl or C 2 -C 6 alkylene together; - ^R5 is C1-4 alkyl, phenyl, (C1-14 alkyl) phenyl, halophenyl, or d- or II () - camphoryl group; characterized in that a) Compound of formula V - X is halogen, Ar and R ¹ are as defined above - R ³ OM is an alkali metal alkoxide - wherein R ³ is as above and M is an alkali metal - R ³ OH - R ³ is as defined above; obsession b) Compound of formula V - Ar, X and R ¹ are as defined above - R ³ OM with alkali metal alkoxide - R ³ and M -151 192 451 is as defined above, then reacting the resulting epoxy compound of formula VII: - Ar, R ¹ and R ³ are as defined above - with an alcohol of formula R ⁴ OH - R ⁴ is as described above - R ⁴ OM is an alkali metal- in the presence of an alkoxide, R ⁴ and M are as defined above; obsession c) reacting a compound of formula V - Ar, X and R ¹ are as defined above - with an alkali metal glycol and then obtaining a compound of formula VI - Ar, R ¹ , R ³ and R ⁴ as defined above - R ₂ O ⁵ vegyülettel- formula -SO2 -Hal or i ^(R5 _-SO2) R ⁵ have the meanings as defined earlier and Hal represents a halogen atom - is reacted. (Priority: 09/09/1981) 2. A process for the preparation of a-sulfonyloxy-ketone acetal derivatives having the following general formula (II): - Ar represents a (C1-C4) alkyl or (C1-C4) alkoxy optionally substituted phenyl; - R ¹ is hydrogen or C 1-4 alkyl; or - Ar and R ¹ together represent 1,2,3,4-tetrahydronaphthyl; - R ³ and R ⁴ are each independently C 1 -C 4 alkyl or C 2 -C 6 alkylene together; - ^R5 is C1-4 alkyl, phenyl, (C1-4 alkyl) -phenyl, halogenophenyl, a d- or 1-10-camphoryl group; characterized in that a) Compound of formula V - X is halogen, Ar and R ¹ are as defined above - R ³ OM is an alkali metal alkoxide - wherein R ³ is as above and M is an alkali metal atom - R ³ OH - R ³ is as defined above; obsession b) reacting a compound of formula V with Ar, X and R ¹ as defined above, with an alkali metal alkoxide R ³ OM, with R ³ and M as above, and then reacting the resulting epoxy compound VII with Ar, R ¹ and R ³ are as defined above, with an alcohol of formula R ⁴ OH - R ⁴ is as defined above - R ⁴ OM is in the presence of an alkali metal alkoxide - R ⁴ and M are as defined above; obsession c) reacting a compound of formula V with Ar, X and R ¹ as defined above with an alkali metal glycol, and then obtaining a compound of formula VI with Ar, R ¹ , R ³ and R ⁴ as defined above - R ⁵ With -SO ₂ -Hal or a compound of the formula (R ⁵ -SO ₂ ) ₂ O - R ⁵ is as defined above and Hal is halogen. (Priority: 9/11/1980) 3. A process for the preparation of a-sulfonyloxy-ketone acetal derivatives having the following general formula (H): Ar is phenyl substituted with chloro or fluoro, phenyl, acetamido, C 1-4 alkoxy optionally substituted with 2 halogens or 1-oxo-2-isoindolinyl, and 2-thienyl or 6-methoxy-2-naphthyl ; - R ¹ is hydrogen or C 1-4 alkyl; or - Ar and R ^{1 taken} together may represent 1,2,3,4-tetrahydronaphthylcarbonyl; - R ³ and R ⁴ are independently C 1 -C 4 alkyl, or together C 2 -C 6 alkylene, -R ⁵ is C 1 -C 4 alkyl, phenyl, (C 1 -C 4 alkyl) phenyl, halophenyl or d-10-camphoryl group, characterized in that a) Compound of formula V - X is halogen, Ar and R ¹ are as defined above - R ³ OM is an alkali metal alkoxide - wherein R ³ is as above and M is an alkali metal - R ³ OH - R ³ is as defined above; obsession b) reacting a compound of formula V with Ar, X and R ¹ as defined above, with an alkali metal alkoxide R ³ OM, with R ³ and M as above, and then reacting the resulting epoxy compound VII with Ar, R ¹ and R ³ are as defined above, with an alcohol of formula R ⁴ OH - R ⁴ is as defined above - R ⁴ OM is in the presence of an alkali metal alkoxide - R ⁴ and M are as defined above; obsession c) reacting a compound of formula V - Ar, X and R ¹ are as defined above - with an alkali metal glycol, and then obtaining a compound of formula VI - Ar, R ¹ , R ³ and R ⁴ as defined above - R ⁵ -SO2-Hal or ^(R5 -SO2) ₂ O in the formula - R ⁵ and Hal have the same meanings jelentése- meanings as is halogen, is reacted.