JPS5883644A - 5-phenyl-2s-pentanol stereospecific synthesis - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention utilizes a readily available optically pure starting material (S
The present invention relates to a method for stereospecifically synthesizing 5-fluorinyl-28-pentanol from (ethyl lactate). This method uses 7-enethyl alcohol at the same time.

A purified product is obtained that is free from contamination of alcohols such as 3-phenylzorobyl alcohol.

These mixed alcohols are difficult to remove, and if not removed, they will cause reponanthradol (Johns
on, U.S. Patent 4, 260.764”, John
son et al., J., Cl1n, Pharmaeol,
21, pp271 S-2822Lw 198
1: Milne, Johnaon same p.
p-367S-3748), making 5-phenyl-28-pentanol incompatible in the synthesis.

This is because the contaminant alcohol participates in the synthesis of leponanthradol, resulting in corresponding contaminants in the cNS agent, e.g. 2-phenylethoxy side chain instead of 5-phenyl-2-pentyloxy side chain. This is because compounds are mixed.

Nantradol, synthesized from 5-phenyl-28-pentanoyl, has been found to have clinical use in humans as an analgesic. (Jain et al.

J, Cl1n, Pharmaeol, pp 32
08-3268.

(1981) It can also be used as an antiemetic in cancer chemotherapy (Lassie et al., PP, 48S-5
3S; Penta et al., pp11s-228: Cr
Onin et al. PP 43 S-50S: J
ohnson.

Milne, U.S. Patent 4.228, 169) Conventionally,
The best stereospecific synthesis of 5-phenyl-28-pentanol used the reaction of phenethylmagnesiumolide with S-propylene oxide; 2
It was almost impossible to produce 8-pentanol, especially in the large quantities required for industrial production of GJS agents such as leponanthradol.
The intermediates used in this synthetic method are known compounds, namely methyl 2S-benzyloxyzolobionate (compound of formula (IV) below) and 28-benzyloxy-1-propatol of formula (V) below. . These compounds were described by Mislowa 4, J.

Am, Chew, Soe, 84, PP-19
40-1944 (1962), the latter compound being reported in its D-form. The first compound was prepared by reaction of methyl S-lactate with benzyl bromide in alcohol in the presence of large amounts of platinum oxide. This method requires the use of expensive reagents, and in this method, expensive platinum oxide is used. Mialov et al. reduced methyl 2S-benzyloxyzolobionate with lithium aluminum deuteride to give 2S-pene, soloxy-1-propanol-1-d2, which was further converted into p-promobenzenesulfonium ester. After that, 28-pencyloxy-1-propatol-1-d3
is being converted to . Compare with equation (IV) below.

The present invention provides chiral (ehi) of the formula: 05-phenyl-28-pentanol.
ral) relates to a stereospecific and advantageous process for the preparation of alcohols. The final step is formula 0 (n
) is a chiral ketone with the formula: h
It is produced by hydrolysis and decarboxylation of chiral ester of Uυυ. The chiral (chtral) benzyl ether-ester of formula (III) is an alkali metal salt of (C□-C4) alkyl benzoyl acetate, for example, the formula: CH3 C, HsCH2-0-C-OH,X-IV)
(wherein,

In formula (IV), X is CI, Br, or IO halide,
It is produced by reacting X with OSO□CR or a metal in the compound of formula (mV). A preferred sulfonate ester is a mesylate ester.

In the compound of formula (IV), X is 080. CH, Matahiro's chiral compound 2S-benzyloxy-
It is prepared by reacting prickly ppanol with methanesulfonyl- or p-)luenesulfonyl chloride. Formula (V
) is a compound of the formula: CH3 C, H, CH, QC: C0OR... (in the formula, R is (C1-04) alkyl). and make it.

On the other hand, in the compound of formula (■), X is CI and Br.

Or Palite of I is a compound of alcohol (V) 80
01.2, PBrl * PI H (D like, /
'Orn (IJL!: 0 benzylated lactic acid ester L1 of formula (VI) produced by reaction) corresponding formula: %formula%) (wherein R is (C1-C4) alkyl),
It can be produced by converting methyl S-lactate into ethyl ether solidified benzyloxy in the presence of a large amount of platinum oxide according to the method of Mlslov. If an inexpensive base such as sodium hydroxide is used in place of platinum oxide, the reaction can be carried out with extensive or complete racemization. Interestingly, benzyl mesylate was heated at about 110-140 °C (1
When the reaction is carried out by heating at a temperature of 20 DEG to 160 DEG C., the chiral benzyl ester of formula (VI) is obtained in high yield. With this method, racemization hardly occurs.

The present invention also provides formulas (n), (m), (IV
) 05-phenyl-28-pentanolyl, which also includes chiral intermediate compounds: country! permission 4
,206,225; 4,232,018; 4,
235.913; 4.243,674: 4.26
0,764; 4.263.438; 4.270,
005:4,283,569, methods for the synthesis of CNS agents such as Shiza Nantradol are also described.

The various steps in the present invention can be performed using readily available and relatively inexpensive starting materials and reagents.

To convert the ehiral ketone of formula (If) to 5-7 aeryl-28-pentanol, the former ehiril ketone can be converted (either directly without a solvent or by dissolving it in a reaction-inert solvent). Catalytic reduction with hydrogen in the presence of a noble metal catalyst (or in suspension) at a suitable temperature until the carbonyl group is converted to methylene and the benzyl group is hydrogenolyzed (if necessary). The target product, 5-phenyl-28-pentanol, is isolated by a conventional method. Generally, the steps include filtration of the catalyst, washing with a suitable solvent, combining the filtrate and washing solution, washing, and distillation. If necessary,
Historically, it is purified by vacuum distillation, but this step is usually not necessary. An outstanding aspect of the present invention is that 5-phenyl-28-
Pentanol can be obtained and is suitable for the synthesis of nantradol and other CNS active agents.

ζThe "reaction inert solvent" used here is a solvent for reactants, reagent products, and a suspension solvent that reacts with the above reactants, reagents, and products to increase the yield of the desired product. It means something that does not decrease.

When hydrogenation is carried out in a solvent, a low boiling point solvent is preferred. This is because the product can be easily obtained by distilling off these solvents, and many operations required for distilling the product are not required. As a suitable solvent, (C, -C,)
Alkanols, ethers (diethyl ether, diisoglobyl ether, tetrahydro-7rane, dioxane,
hydrocarbons (such as 1,2-dimethoxyethane), hydrocarbons (such as toluene), and halodanated aliphatic hydrocarbons (ethylene chloride). It is good to add at least a portion of a protic solvent (for example, water or (C□-C41 alkanol). Also, the removal of the benzyl group of the formula by catalytic hydrogenolysis and the hydrogenation of the alcohol intermediate are promoted. For this purpose, it is recommended to add a portion of a strong acid (for example, hydrochloric acid).The solvent used for hydrogenation is suitable for filtration and recovery of the catalyst.

The temperature and pressure of hydrogenation are not limited. Wide range of temperatures 1,
(for example, 0-75°C) and pressure (from around normal pressure to 100 atmospheres or more) may be used depending on the catalyst system. In general, hydrogenation requires no complex equipment, rounding, low pressure (
For example, it is preferable to perform this at a pressure of 1-7 atmospheres). Room temperature (for example TF15
-25°C) is generally preferred for KJIL. If the catalyst temperature is low, high temperatures are required, but from an economical standpoint, high temperature conditions are used.

Using a catalyst with low activity requires high pressure (i.e. above 7 atm) and high temperature (above 25°C) to obtain a good reaction rate.
It is understood that this is necessary.

The noble metal catalyst used in the present invention may be platinum, palladium, rhenium, rhodium or ruthenium and may be used with or without a support or in the form of known compounds such as oxides and chlorides. Suitable catalyst supports are carbon, silicon, barium sulfate. The catalyst may be used as is, or the salt of the catalyst compound may be reduced beforehand. This can be easily accomplished by suspending the catalyst precursor in a reducing solvent and reducing it before adding the substrate, followed by catalytic reduction. Alternatively, you can mix everything together and absorb the bulk of the water. The former method is advantageous because the catalyst is reduced in advance and the substrate is reduced, so that the hydrogen absorption amount can be determined separately. A good noble metal catalyst for this method is one using palladium as a support. A good support is carbon. The amount of palladium in the support is not limited but is generally 0 using 5-10% by weight, or more or less using 0. For convenience of operation, the catalyst preparation is
Generally, it is "water-wet" containing an amount of water equal to the weight of precious metal and support (e.g., 50 cm wet). A good catalyst works well at low pressure and temperature, especially when a protic solvent is used in part and a small amount of a strong acid is used.

The kyl ketone of formula (II) is produced by hydrolyzing and decarboxylating the corresponding ester of formula (m).

Both bases and acids are used as catalysts for hydrolysis and decarboxylation. Polar protic solvents, e.g. water'% (CI-C,)
Base catalysis using lower alkanols or mixtures thereof is preferred. A zero incubation, where alkali metal hydroxides are good base catalysts and potassium hydroxide is the best, generally
For example, heating to 60-100° C. is performed to obtain a good reaction rate without decomposition of the reactants or products. A good solvent system is water:ethanol, 50:50 by volume; 7
The reaction is carried out under reflux at 9-80°C. The reaction is carried out under these reaction conditions until both hydrolysis and decarboxylation are completed.

i.e. the formula: The acid intermediate of is not isolated.

Esters of formula (m) are X(CI) of compounds of formula (IV)
, Br, I, 080. CH3,0803-C)
-CH3> is prepared by carrying out a nucleophilic substitution reaction with the anion of a (C, -C4) alkylbenzoyl acetate ((C1-C4> used in the form of an alkali metal salt, particularly the sodium salt) of the alkylbenzoyl acetate.

Solvents such as alcohols, acetonitrile, dimethylformamide, etc. are suitable for this reaction.These solvents must be inert to the reactants and products, and must be present in the presence of the reactants. In order to maintain a high concentration of the anion to be used, the benzoyl acetate ester must also be of low acidity. The silver needs to be high enough to give good reaction rates, but
As is well known, the reaction rate varies depending on the nature of X (for example, I) Br > CI), the solvent, the type of R, and the alkali metal salt used.

The reaction time should be such that the reaction is complete and gives the highest yield (e.g. >95% when using equivalent amounts of compound (IV) and alkyl benzoyl acetate salts).
For example, from 1 hour to several days depending on the temperature). These reactions are easily checked by thin layer chromatography using a commercially available silica gel plate containing an ultraviolet indicator. A suitable developer is a hexane-ethyl acetate mixture; for example 6:1 hexane:ethyl acetate. As the reaction progresses, an equivalent amount of strong base is neutralized. This is because pH is a means of checking the reaction.

Since the nucleophilic substitution reaction occurs quickly and cleanly, a good X is I. In this case, dimethylformamide is a good solvent and the reaction is carried out at L120-126°C for about 2 hours. When X is other than I, the use of iocide ion promotes the progress of the reaction. This is because it has the effect of forming Wll iodide as an intermediate in the reaction system.

X is CI, Br or! It is produced by a nucleophilic substitution reaction of a chiral ester of formula (IV). The reaction conditions described above can be adapted in this case. To prepare organic iodides from good mesylate, the mesylate ester in acetone is mixed with excess sodium iodide (15-2.5 equivalents) for 20
Chiral (IV) refluxing for ~24 hours
) The sulfonate ester can be prepared by conventional methods in the sulfonation of alcohols, for example, by adding an equivalent amount of organic sulfonyl p
The ride is prepared in an inert solvent at room temperature or at low temperature (-
Good solvents are those with low boiling points (e.g. methylene chloride) that can be easily removed by distillation (e.g. methylene chloride).
al) alcohol as described in Example 6 below;
It is prepared by hydride reduction of O-benzyl lactate of formula (VI), and similarly by reduction of methyl O-benzyl lactate with lithium aluminum deuteride, as done by Mislov et al. Hydride reduction of esters of formula (VI) can be carried out using various hydride reducing agents, such as water-bulked lithium aluminum (as such or in a 50% suspension in oil), rRed-al J (in benzene, hydrogenated bis( (2-methoxyethoxy)aluminum 70% solution), water-enriched sodium or lithium. When lithium aluminum hydride is used, the solvent used is essentially a solvent that is non-Gutonic and has dangerous groups to be reduced (carbonyl group, nitrile, nitro, aliphatic halide, sulfonate, etc.). Good ones include nato-2hydrofuran, dioxane, 1,2-dimethoxyethane,
Bis(2-methoxyethyl) ether. Re
When using d-alt, aromatic hydrocarbons such as benzene or toluene are good solvents. Grotonic solvents such as sodium borohydride ethanol generally need to be used.

It is an object of the present invention to convert the chiral (C1-C4) alkyl lactate of formula (■) into its 0-benzyl derivative without causing racemization and without using expensive platinum oxide as a catalyst. Interestingly, this reaction does not contain benzyl mesylate in excess of chelate #
(ehiral) (CI C4) in an alkyl lactate ester (e.g. about 3 equivalents) heated at 80-110 DEG C. for 1-4 hours depending on the reaction temperature used. Excess lactic acid ester can be separated by distillation, but it is better to convert this contaminant into propylene glycol, which is easily soluble in water, in the next step, and converts it into 2-pencyloxy-1-f lovanol (V).
Benzyl mesylate, which can be easily removed by extraction, is produced by reacting benzyl alcohol and methanesulfonyl chloride in the manner described above.

The present invention is illustrated by the following examples. However, it is to be understood that the invention is not limited to the details of these examples.

Example 1 Bensyl Methanesulfonate Benzyl alcohol (129,6r, 1.2 moles) and hydrethylamine (182F, 'L8 moles) are mixed in methylene chloride (14 liters) under nitrogen gas. This is cooled to -5°C in an ice-water-acetone bath while stirring. A solution of methanesulfonyl chloride (15 (1,131 mol)) dissolved in 100-methycin 05ide is added over 49 minutes while maintaining the temperature at -5°C to 2°C.

After stirring for 10 minutes at 0-2℃,
Dilute with water cooled to °C. The organic layer was separated, washed with cold water (2 x 500 m/), dried over a Mg field, filtered and evaporated under vacuum to give the title compound as a pale yellow oil. (
190F, 85chi, H-Hatokan (CDCl2) Delta (
PPm): 2.9 (8,3H).

5.2 (8, 2H), 7.4 (m, 5H)
;RfO,75(CH2Cl,) ) This product □ is stored in the refrigerator until used in the next step.

Example 2 Ethyl 28-pendyloxyglobionate Benzyl methanesulfonate under nitrogen gas.

(1B1.5y, 0.975 mol) was mixed with S ethyl lactate (ethyl 2S-hydroxypropionate; 59
5f, mixed with 3.55 morn. Heat the solution to 94° C. for 15 minutes on a steam bath and keep warm for 1.5 hours. Cool the mixture to 45° C. and pour into 2 liters of chilled toluene. Add water (500 sd) and stir for 5 min. Separate the aqueous layer and extract with fresh toluene of 200 sd. NaHCO3,2x 500w
The crude product was washed as an oil as an oil by washing with 100 g of water and 1 x 508 of saturated NaCl, drying over Mg5O, filtration, and evaporation in vacuo. The initial solvent evaporation edge, min 1ii1 (25
m, b,, 79°/12■; [Alpha] D-6,9'
:C=1.13 (CHCl3) :min m2m2-8(
74,b,, 82℃/1.6■-114℃/6■: [Alpha) D-42,10--76,20,C= 1.0
Fraction 9-12 (57/: bp, 1
15V3■, 98-100℃10.75■, 102-1
06℃/1.0 points: [Alpha) D-80,8°~-8
3.7 DEG C., C1,01-1,17 (CHCl3)) The pure title compounds are obtained in each case. In addition, high boiling point substances are 49
f can be obtained. Fraction 10 was dissolved in 100 mg of hexane and fractionated with 30- H,O to remove a small amount of ethyl lactate.
After drying with g5o4, it is filtered and concentrated to obtain an oil. (
2,4y;Rf O,! 12 (6:1 hexane:ethyl acetate); [alpha)D-Eu2O.

C=t13 (CHCl3)).

Example 6 2S-benzyloxy-1-propatol Example 20 Fractions 2-9 and 12 (total amount 105.1f).

Q, 45 moles of ethyl 2S-benzyloxyfa bionate and 0.25 moles of S-ethyl lactate) are dissolved in 100-mole of absolute ethanol. The above solution is added to a mixture of 500% absolute ethanol and N1.4 (3z85f, 10 moles) over a period of 1 hour under nitrogen gas. During the addition, keep at 25-30°C in a 20°C water bath. After stirring at room temperature for 20 hours, the reaction mixture was cooled to 10°C and diluted with 95-12N
HC1 (114 mol) is added dropwise over 15 minutes under nitrogen gas. The resulting slurry is filtered and washed with 100-ml ethanol. Combine the R solution and cleaning solution and heat under vacuum for 15 minutes.
Concentrate to 0 mg. Dilute this with 200-ml water,
Furthermore, 600-ethyl acetate was added and 4N NaOR,
Adjust the precipitated solids to pH 90 at 50 wt) and separate the layers. Water layer 1 x 100 m, l x 50-
Extract twice with ethyl acetate. Combine organic layers to form 2X1
After washing with 50-H and 150-I of saturated brine, drying over MgSO4, filtration and evaporation, the title compound is obtained as an oil.

(cHcI3):+27.736 (=-t);Rf
o, 1(CH,Cl2)).

Example 4 28- was converted into 2S-benzyloxy-1-glopanol (49,
8f, 0. ! t mol), 400-CH, Cl2t
) 9 engineering fk7 min (40.5 t, 0.4 vol) were mixed and stirred while cooling to -5°C in an ice-water-acetone bath. While keeping at -5℃, methanesulfonyl chloride (37.8F, 166%)
Add ICH, CI2 solution over 1 hour ◎ -5℃
After stirring for 0.5 h at , H,0 (200 mg at 5° C.) is added. Separate the layers and add the aqueous layer to 1 x 100-cH2C1
Wash with □. The merged organic layers are sequentially IXllXl
oOs H, 0, lX100 - lNHCl, lX10
0mg N20. lX100-saturated NaH■, e
After washing each with 1×100 of N20 and drying over Mg8o4, filtration and evaporation under vacuum gives the title product as an oil (72,2r.

98.5chi, [alpha)D+7.7, C=100(
cHcI3);RfO,6(cH2C12)).

Example 5 Iodination 2S-Benzoloxy-1-globil Sodium iodide <909°α6 mol) is dissolved in 1 liter of dry acetone with stirring under nitrogen gas. 28 at 62℃
-bensyloxy-1-propyl mesylate) (71
5F, 0.29·3 mol) is added. 59% of the reaction mixture
Warm to -60°C (mild reflux). This was held for 20 hours, after which time it was checked with tle and approximately 205 G of starting material remained. Furthermore, sodium iodide (!tOf
.

12 mol) and continue refluxing for 6 hours. Cool to room temperature, filter and wash with acetone. Combine P solution and washing solution and concentrate to obtain a wavy solid.

This is diluted with 600-m of toluene and 200-m of H,0, the layers are separated and the aqueous layer is extracted with 2×100-st of toluene. The organic layers were combined, washed with 2 x 200 wl OH,O, and dried with Mg5O. This is filtered and evaporated to give the title product as an oil.

(79f, 9696: (alpha)D+8.0°, c=
t 08 (cHcI) -H-width-(CD
Cla) Chill fi (Ppfll), 14 (
d, 3H), 3-3°6 (m, 5H).

4.6 (S, 2H), 7.55 (S, 5H))
Example 6 Ethyl 2-benzoyl-48-pensyloxyvalerate Sodium hydrogen (50% in oil) under nitrogen gas.

13.6F, 0.283%) tf of tr5X2DDw
Add 130-dimethylformamide to the NaHII suspension in hexane, which is washed with Jl hexane. next,
Ethyl pembyl heptatate (54,4F, 0.2
83 mol) in a 10°C water bath over 45 minutes.
While keeping the temperature at -52°C, add dropwise with % N2 gas while discharging the generated N3. After stirring at 025°C for 8 minutes, 2S-bensiloxy-1-propyl iodide<78? , 0.28
5 mol) and 4o-zomethylformide. The reaction mixture is heated and stirred at 122-126°C for 2 hours. (During this time a solid precipitates out.) It is cooled to 70°C, diluted with 65° toluene and 560° ice water, and the layers are separated. The aqueous layer was extracted with 3X 150-H toluene, the organic layers were combined and 3X 150-H,0°1
After washing with saturated NaCl of X150-, drying with Mg5o4. This was filtered and evaporated under vacuum to obtain the title product as an oil (90f, 905G (alpha) D+
15.80. C=112 (CHCI, ): R
f O, 35 (6:1. hexane: ethyl acetate)] Example 7 48 hensyloxy-1-phenyl-1-pentanone ethyl 2-benzoyl-48-bensyloxyvalerate
(89f, 0.26 mol), ethanol (175
mg), water (175+d), KOH (85%.

51F, 0.8 mol) is mixed with stirring under a nitrogen blanket. During this time the reaction temperature rises to 45°C. The reaction mixture is heated to reflux at 79°C and maintained at this temperature for 18 hours. The reaction mixture is cooled to 25°C and diluted with 650° of water and 300° of toluene. Separate the layers and transfer the aqueous layer to lX2005
g, wash with 2X150st toluene. Combine the organic layers and add 2X200-〇H,0,lX200-saturated Na
After washing with C1 and drying with Mg5o4, filtration and concentration in vacuo give the title compound as an oil. (45,5
F, 65-[alpha) +21.92°, C=
1.20 (CHCI3); Rfo, 55 (6:
1 H-Vsan: ethyl acetate).

Example 8 5-Phenyl-28-pentanol 150- to a solution of 4S-benzyloxy-1-phnyny-1-pentanone (45f, 0.168 mol) in toluene, 15m absolute alcohol with 6 drops of concentrated hydrochloric acid and using 4t of 50-moist p4/C, 50 pai
g. After 06 hours of hydrogenation at 25° C., add another 4 t of catalyst and add water for 2.5 hours. At this point, 3 equivalents of hydrogen are consumed and no hydrogen is absorbed during the final 1.51 iIf. The catalyst was removed by filtration, and the liquid was mixed with solid N.
aHα) Neutralize with 15 cc. After drying over Mg804, filtration and concentration in vacuo afford the title product as an oil. (22t t(CHCI,) :Rf=0.2
(6:1 hexane:ethyl acetate>) If necessary, further distill the labeled product to remove any standing tie origin material.

bp, 90-94℃/Q, 7 wm s (quantitative) 0 Patent applicant 4 people other than Fiday Incorporated Continuation of 1st page oInt, C1, 3 Identification code Office reference number C0
7C1411087162-4H //B 01 J 23/40
7624-4GC07D 221/10
6675-4C priority claim 01982 8
May 5th ■United States (US)■404075 0 Inventor Pernat Shields Moore 39 Savvy Avenue, Waterford, Connecticut, United States of America

Claims (1)

[Claims] 1. A method for producing a 2S chiral alcohol of the formula: which comprises hydrogenating a chiral ketone of the formula in the presence of a noble metal catalyst. Hydrogenation of a compound with a noble metal catalyst; and formula (b): (wherein R is (C□-C,)alkyl) chiral (eh
A process for the preparation of a 2S chiral alcohol of the formula: characterized by: preparation of a chiral ketone of the formula (1) by hydrolysis and decarboxylation of an ester. 3. Hydrogenation of a chiral ketone of the formula (a) with a noble metal catalyst:
iral) Formula by hydrolysis and decarboxylation of ester ■
Production of chiral ketones: (c)
(Alkali metal salt of CI-04' alkyl benzoyl acetate and formula: % formula % (wherein, X is I, Brt C1t 08O1CH3
chiral of formula (m) by reacting with or, optionally in the presence of shodate ions.
Preparation of esters: by reaction of sulfonate ester compounds with halide ions of the formula
); (e) methanesulfonyl chloride or P-toluenesulfonyl chloride by reaction with a chiral compound of the formula %(), in which X is a sulfonate ester; Production; (0 formula: % formula % (): (in the formula, 8 is (C□-d4) alkyl) chiral (ch
formula (iral) by reduction of the ester with hydride (
V) Preparation of chiral compound;-)
Benzyl methanesulfonate with the formula % formula % formula % (2) (wherein R is (C, -C,)7A4) in chiral (eh
formula (V
I) Preparation of a chiral ester of the formula: A process for the preparation of a 2S chiral alcohol of the formula: 4. Benzyl methanesulfonate its tt and excess formula: % formula % (wherein R is (C, -C4) alkyl) chiral (eh
xyl (c
hiral) Production method of ester. 5. A chiral ketone of the formula: (wherein Y is hydrogen or -COOR"t' and LR is (C. -C4) alkyl). 6. The chiral ketone of claim 5, wherein Y is hydrogen. (chiral) ketone. 7. Chiral (chn Hatake 1) ketone 08 according to claim 5, wherein Y is -COOR and R is ethyl.
Formula: %Formula%: (In the formula, X is I, Br, CI, or 1iO8O2cH3
) chiral compounds. 9. Xyl according to claim 8, in which X is I (
chiral) compound. 10, X KA0802CH3f 4. The chiral compound of claim WJ8.