NZ212464A - Laevorotatory enantiomers of propionic acid derivatives - Google Patents

Description

New Zealand Paient Spedficaiion for Paient Number £12464 ; Priority Date(s): <£^.7 .........

Complete Specification Filed: Class: CQJC&.j.COJty?.) Co 7 c\2Y Publication Date: P.O. Journal, No: 1219.

Under the provisions of Regtf* lation 23 (!) the Cowpjefe - Specification has been ante-dstedj toJLL Initials N.Z. No.

NEW ZEALAND Patents Act 1953 COMPLETE SPECIFICATION "LAEVOROTATORY ENANTIOMBRS OF PROPIONIC ACID DERIVATIVES." We, BAYER AKTIENGESELLSCHAFT, a Company registered under the laws of the Federal Republic of Germany, of Leverkusen, Germany, do hereby declare the invention, for which we pray that a Patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement : - •" 1 ~ (Followed by 1A.) - 1A - The present invention relates to laevorotatory enantiomers of propionic acid, a process for their production Broadly, the present invention provides laevorotatory enantiomers of propionic acid derivatives of the formula in which Z represents tosyl or «esyl, Y represents oxygen or the radical S0n, whe rei n ■ represents 0, 1 or 2, R^ represents hydrogen or methyl, n represents 1 or 2 and r' and R* Independently of one another represent hydrogen, halogen, alkyl with 1 to 4 carbon atons, alkoxy with 1 to * carbon atons, alkylthlo with 1 to 4 carbon atons, nitro, cyano or alkoxycar-bonyl with 1 to 4 carbon atons 1n the alkoxy group.

The present invention also provides a method of preparing compounds of the formula I by reacting hydroxy compounds of the formula • // HO-CH-(CH2)n-Y-CH2-' (II in which 2 3 4 R , R , R , Y and n have the abovementioned meaning, with laevorotatory enantiomers of lactic acid derivatives of the formula CH3 Z-0-CH-C0-C1 (III) * in which Z represents tosyl (~S02—or mesyl (-SC^-CH^) , if appropriate in the presence of an acid acceptor and if appropriate in the presence of a diluent.

The hydroxy compounds of the formula (II) required as starting substances in the preparation of the laevorotatory enantiomers of propionic acid derivatives of the formula (I) are known, or they can be prepared in a simple manner by known methods. The laevorotatory enantiomers of lactic acid derivatives of the formula (III) also required as reaction components in the reaction for the synthesis of compounds of the formula (I) are known, or they can be prepared in a simple manner by known methods.

The process for the preparation of substances of the formula (I) are preferably carried out using diluents.

Possible diluents for this are virtually all the inert organic solvents. These include, preferably, aliphatic and aromatic, optionally halogenated hydrocarbons, such as pentane, hexane, heptane, cyclohexane, petroleum ether, benzine, ligroin, benzene, toluene, xylene, methylene chloride, ethylene chloride, chloroform, carbon tetrachloride, chlorobenzene and o-dichlorobenzene, ethers, such as diethyl ether and dibutyl ether, glycol dimethyl ether and diglycol dimethyl ether, tetrahydrofuran and dioxane, ketones, such as acetone, methyl ethyl ketone, methyl isopropyl ketone and methyl isobutyl ketone, esters, such as methyl acetate and ethyl acetate, nitriles, such as, for example, acetonitrile and propionitrile, amides, such as, for example, dimethylformamide, dimethylacetamide and N-methyl-pyrrolidone, and dimethylsulphoxide, tetramethylenesulphone and hexamethylphosphoric acid triamide. 2 12464 Acid acceptors which can be used in the process for the preparation of compounds of the formula (I) are all the acid-binding agents which can usually be employed for such reactions. Preferred acid acceptors are alkali metal hydroxides and alkaline earth metal hydroxides and oxides, such as, for example, sodium and potassium hydroxide, calcium hydroxide and calcium oxide, alkali metal carbonates and alcoholates, such as sodium and potassium carbonate and sodium and potassium methylate or ethylate, and furthermore aliphatic, aromatic or heterocyclic amines, for example triethylamine, trimethylamine, dimethylaniline, dimethylbenzylamine, 1,5-diazabicyclo[4,3,0]non-5-ene (DBN), 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU) and pyridine.

The reaction temperatures can be varied within a substantial range. In general, the reaction is in each case carried out at temperatures between -20°C and +160°C, preferably between -10° and +100°C.

The process according to the invention is in general carried out under normal pressure. However, it is also possible to carry out the process under increased or reduced pressure.

For carrying out process according to the invention, the particular starting substances required are in general employed in approximately equimolar amounts. However, it is also possible to use one or both of the particular components employed in a larger excess. The reactions are in general carried out in a suitable diluent in the presence of an acid acceptor, and the reaction mixture is stirred at the particular temperature required for several hours. Working up is in each case effected by customary processes. In general, a procedure is followed in which water is added to the reaction mixture and the mixture is extracted with an organic solvent of low water-miscibility and the combined organic phases are dried and concentrated by stripping off the solvent.

Some of the new compounds are obtained in the form of oils, some of which cannot be distilled without decomposition, but can be freed from the last volatile constituents by so-called "incipient distillation", that is to say by prolonged heating to moderately elevated temperatures under reduced pressure, and can be purified in this manner.

Preparation Example 1 ch, Tos-O-CH-* :-o-ch2-ch2-o-ch2 o (1) .25 g (0.02 mol) of the laevorotatory enantiomer of lactyl chloride tosylate were added to a mixture of 3.32 g (0.02 mol) of glycol monobenzyl ether, 2 g (0.02 mol) of triethylamine and 50 ml of toluene at 20°C, while stirring. Stirring was continued at 70°C for 14 hours and the reaction mixture was then worked up by adding 100 ml of water, extracting the mixture several times with toluene and drying the combined organic phases and concentrating them by stripping off the solvent under reduced pressure. 6.3 g (80.5 X of theory) of the laevorotatory enantiomer of (2-benzyloxy)-ethyI 2-tosyloxy-propionate were obtained in this manner.

Optical rotation: * -10.2° (1 molar solution in chloroform; cell length * 10 cm).

The substances of the formula (I) listed by way of their formulae in the table I which follows were synthesised by the method for the preparation of the compound described in the preparative Example. 212464 Table i (I) Example Z R2 n Y R3 R4 Optical 7&T Tos h 1 0 2-f h - 9.7 Tos h 2 0 h h - 10.3 Tos ch3 1 0 h h - 4.1 Tos H 1 0 4-ci h - 7.6 Tos H 1 s h h - 10.9 The compounds according to the present invention are useful as intermediates for the preparation of optically active phenoxy propionic acid derivatives which compounds and processes for their production are described in New ' ■ J <'/■ fV 2 124 64

Claims (4)

WHAT WE CLAIM IS:

1. Laevorotatory enantloners of propionic acid derivatives of the fornula CH3 O R2 Z-O-CH C-O-CH-(CH-) -Y-CH, * 2 n 2 R"" in which Z represents tosyl or nesyl, Y represents oxygen or the radical S0m, wherei n n represents 0, 1 or 2, 2 R represents hydrogen or nethyl, n represents 1 or 2 and R3 and R* independently of one another represent hydrogen, halogen, alkyl with 1 to 4 carbon atoms, alkoxy with 1 to 4 carbon atoms, alkylthio with 1 to 4 carbon atoms, nitro, cyano or alkoxycar-bonyl with 1 to 4 carbon atoms in the alkoxy group.

2. Process for the preparation of laevorotatory enantloners of propionic acid derivatives of the fornula CH3 O R* Z-O-CH C-O-CH- (CH-) -Y-CH • * n (I) 2 12464 - 7 - In which I represents tosyl or nesyl, Y represents oxygen or the radical S0n, whe rei n m represents 0, 1 or 2, y Rfc represents hydrogen or nethyl, n represents 1 or 2 and R3 and R^ Independently of one another represent hydrogen, halogen, alkyl with 1 to 4 carbon atoms, alkoxy with 1 to 4 carbon atoms, alkylthio with 1 to 4 carbon atons, nitro, cyano, or alkoxycai— bonyl with 1 to 4 carbon atoms in the alkoxy group, characterised in that hydroxy compounds of the fornula 1n wh1ch J * / R , R% R , Y and n have the abovementioned neaning, are reacted with laevorotatory enantiomers of lactic acid derivatives of the formula ch3 z-o-ch-co-cl (iii) in which Z has the abovementioned neaning, if appropriate in the presence of an acid acceptor and if appropriate In the presence of a diluent. - 8 - 212464

3. An enantionmer according to claim 1 substantially as hereinbefore described or exemplified.

4 . A process according to claim 2 substantially as hereinbefore described or exemplified. BAYER AKTIENGESELLSCHAFT By Their Attorneys HENRY HUGflES LIMITED By: W.O 1H>* i /