Claims
- 1. Process for the preparation of 2-thienylethylamine derivatives of general formula: ##STR8## as well as their acid addition salts, in which R represents a halogen atom and R.sub.1 represents a C.sub.1 -C.sub.4 alkyl group wherein a thienylglycidic derivative of general formula: ##STR9## in which M represents an alkali metal atom or a fraction of an alkaline-earth metal atom, is reacted with a phenylglycine ester, optionally in the form of a strong acid salt, of general formula: ##STR10## in which R and R.sub.1 have the same meaning as above, in the presence of an alkali metal borohydride of general formula:
- X--Y IV
- in which X represents an alkali metal atom and Y represents a group of formula:
- --BH.sub.3 CN or --BH.sub.(4-w) Z.sub.w
- in which Z represents a carboxylic acid residue and w represents 1, 2 or 3, which gives the desired compound in the form of a free base which can be treated, if necessary, with an acid in order to obtain an addition salt of this compound.
- 2. Process according to claim 1 wherein the halogen atom is situated at the ortho position.
- 3. Process according to claim 1 wherein the halogen atom is chlorine.
- 4. Process according to claim 3 wherein R.sub.1 represents methyl.
- 5. Process according to claim 4 wherein the 2-thienylethylamine derivative of formula I and the phenylglycine ester of formula III are each in (+)-(S) enantiomer form.
- 6. Process according to claim 1 wherein M represents lithium, sodium, potassium, calcium 1/2 or magnesium 1/2.
- 7. Process according to claim 1 wherein the phenylglycine ester of formula III is in the form of a strong acid salt chosen from hydrochloride or methanesulphonate.
- 8. Process according to claim 1 wherein Z represents a carboxylic acid residue of general formula:
- R.sub.2 --CO.sub.2 --
- in which R.sub.2 represents a C.sub.1 -C.sub.10 alkyl group.
- 9. Process according to claim 1 wherein the alkali metal borohydride corresponds to sodium cyanoborohydride.
- 10. Process according to claim 9 wherein the reaction is carried out in the presence of a C.sub.1 -C.sub.4 alkylcarboxylic acid.
- 11. Process according to claim 10 wherein the carboxylic acid is used at a concentration not exceeding 0.50 mol/l.
- 12. Process according to claim 11 wherein the carboxylic acid is used at a concentration of 0.30 to 0.35 mol/l.
- 13. Process according to claim 9 wherein the carboxylic acid is acetic acid.
- 14. Process according to claim 9 wherein the phenylglycine ester of formula III is in the form of a strong acid salt.
- 15. Process according to claim 1 wherein the thienylglycidic derivative of formula II is used in excess, up to an additional 0.5 mol per mol of phenylglycine ester of formula III.
- 16. Process according to claim 1 wherein the alkali metal borohydride coresponds to a compound of formula IV in which Y represents the --BH.sub.(4-w) Z.sub.w group.
- 17. Process according to claim 16 wherein the reaction is carried out in a C.sub.1 -C.sub.4 alkylcarboxylic acid.
- 18. Process according to claim 16 wherein the phenylglycine ester of formula III is used in excess up to 2.2 molar equivalents per molar equivalent of thienylglycidic derivative of formula II.
- 19. Process according to claim 1 wherein the alkali metal borohydride of formula IV is used at a concentration not exceeding 0.40 mol/l.
- 20. Process according to claim 5 wherein methyl (+)-(S)-.alpha.-(2-thienyl-2-ethylamino)-.alpha.-(2-chlorophenyl)acetate is prepared.
Priority Claims (1)
Number |
Date |
Country |
Kind |
97/02621 |
Mar 1997 |
FRX |
|
Parent Case Info
This application ia a 371 of PCT/FR98/00441 Mar. 5, 1998.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
PCT/FR98/00441 |
3/5/1998 |
|
|
9/2/1999 |
9/2/1999 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO98/39322 |
9/11/1998 |
|
|
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Non-Patent Literature Citations (2)
Entry |
Dullaghan et al., Journal Organic Chemistry, vol. 17, 1183-1186 (1952). |
Browne et al., Journal Organic Chemistry, vol. 17, 1187-1193 (1952). |