Method for preparing enantiomerically enriched
View Patent ↗This disclosure relates to methods for preparing an enantiomerically enriched N-carboxyanhydride of an amino alpha acid of the formula (IIIa) or (IIIb): from a compound of the formula (IIa) or (IIb), respectively: wherein R1, R2, and R3 are as defined in the disclosure.
1. A method for preparing an enantiomerically enriched α-amino acid N-carboxyanhydride of formula (IIIa) or (IIIb):
from the compound of formula (IIa) or (IIb) respectively:
wherein in the formulae:
R1 and R2 denote, independently of one another, an alkyl, alkenyl, cycloalkyl, alkylcycloalkyl, alkylaryl or aryl group; and
R3 denotes an alkyl or alkylaryl group;
comprising the following steps:
(i) bringing the compound of formula (IIa) or (IIb) respectively into contact with SOCl 2 in a solvent;
(ii) precipitating the N-carboxyanhydride formed in step (i) using a non-solvent; and
(iii) recovering the N-carboxyanhydride,
and not comprising any recrystallization step, nor a sublimation step of the N-carboxyanhydride.
2. The method according to claim 1 , wherein R3 denotes a methyl or ethyl group.
3. The method according to claim 1 , wherein R1 and R2 denote, independently of one another, a methyl or ethyl group.
4. The method according to claim 2 , wherein R1 and R2 denote, independently of one another, a methyl or ethyl group.
5. The method according to claim 1 , wherein R1, R2 and R3 denote a methyl group.
6. The method according to claim 1 , wherein the compound of formula (IIa) is prepared according to the following reaction:
in the presence of a base.
7. The method according to claim 1 , wherein the compound of formula (IIb) is prepared according to the following reaction:
in the presence of a base.
8. The method according to claim 6 , in which the reaction constitutes a step preceding step (i).
9. The method according to claim 7 , in which the reaction constitutes a step preceding step (i).
10. A method of preparing enantiomerically enriched N-carboxyanhydride of formula (A) or (B):
comprising the following steps:
(i) bringing the compound of formula
or respectively
into contact with SOCl 2 in a solvent;
(ii) precipitating the N-carboxyanhydride formed in step (i) using a non-solvent; and
(iii) recovering the N-carboxyanhydride;
and not comprising any recrystallization step, nor a sublimation step of the N-carboxyanhydride.
11. The method according to claim 1 , wherein the reaction from step (i) is carried out at a temperature between −10 and 50° C.
12. The method according to claim 10 , wherein the reaction from step (i) is carried out at a temperature between −10 and 50° C.
13. The method according to claim 1 , wherein the reaction from step (i) is carried out with 1 to 3 equivalent(s) of SOCl 2 relative to the compound (IIa) or (IIb) respectively.
14. The method according to claim 10 , wherein the reaction from step (i) is carried out with 1 to 3 equivalent(s) of SOCl 2 relative to the compound (C) or (D) respectively.
15. The method according to claim 1 , wherein the non-solvent from step (ii) is a liquid alkane or an oil cut.
16. The method according to claim 10 , wherein the non-solvent from step (ii) is a liquid alkane or an oil cut.
17. The method according to claim 1 , wherein the solvent is a chlorinated solvent and the non-solvent is a liquid alkane or oil cut.
18. The method according to claim 1 , wherein the solvent is dichloromethane and the non-solvent is n-heptane.
19. The method according to claim 10 , wherein the solvent is dichloromethane and the non-solvent is n-heptane.
20. The method according to claim 1 , wherein the recovery of the N-carboxyanhydride from step (iii) is a filtration/drying operation.
21. The method according to claim 10 , wherein the recovery of the N-carboxyanhydride from step (iii) is a filtration/drying operation.
22. A compound of formula: