Claims
- 1. A method for stereospecifically preparing a 2-substituted ethyl-2-amine, having chirality at the 2-position, comprising
- (A) reacting a 2-amino-2-substituted ethyl alcohol, having chirality at the 2-position, with an halide or anhydride in the presence of a base to form an 2-substituted aziridine having chirality at the 2-position;
- (B) reacting said aziridine with an lithium compound to form the lithium salt of an 1-2-substituted alkyl-2-amine having chirality at the 2-position; and
- (C) treating said lithium salt with one or more strong acids in the presence of an electrophilic scavenger.
- 2. A method according to claim 1 for preparing a compound of formula ##STR6## wherein * indicates a chiral carbon atom,
- R.sub.1 is optionally substituted aryl, or optionally substituted heteroaryl; and
- R.sub.3 is optionally substituted alkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, or optionally substituted heteroaralkyl; comprising
- (A) reacting a compound of formula ##STR7## with a compound of formula
- R.sub.2 --SO.sub.2 --R'
- wherein
- R' is halo or OSO.sub.2 R.sub.2 ; and
- R.sub.2 is optionally substituted aryl, or trihalomethyl,
- in the presence of a base to form an aziridine compound of formula ##STR8## (B) reacting said aziridine compound with a compound of formula Li--R.sub.1, to form a lithium compound of formula ##STR9## or an aggregate thereof wherein
- R.sub.1 is optionally substituted aryl, or optionally substituted heteroaryl;
- R.sub.2 is optionally substituted aryl, or trihalomethyl; and
- R.sub.3 is optionally substituted alkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, or optionally substituted heteroaralkyl; and
- (C) treating said lithium compound with a strong acid or mixture of strong acids in the presence of an electrophilic scavenger.
- 3. A method according to claim 2 wherein the reaction of step (A) occurs in an aprotic organic solvent.
- 4. A method according to claim 3 wherein said aprotic organic solvent is tert-butyl methyl ether.
- 5. A method according to claim 2 wherein R.sub.2 --SO.sub.2 --R' is p-toluenesulfonyl chloride.
- 6. A method according to claim 2 wherein said reacting occurs at about 25.degree. C. to about 90.degree. C.
- 7. A method according to claim 2 wherein said reacting occurs at about 25.degree. C. to about 40.degree. C.
- 8. A method according to claim 2 wherein said base is selected from the group consisting of an aqueous alkali metal hydroxide, an aqueous alkali metal carbonate, and an aprotic organic amine.
- 9. A method according to claim 2 wherein said base is aqueous sodium hydroxide.
- 10. A method according to claim 2 wherein R.sub.1 is optionally substituted heteroaryl.
- 11. A method according to claim 10 wherein R.sub.1 is 3-chlorothien-2-yl.
- 12. A method according to claim 2 wherein R.sub.3 is alkyl.
- 13. A method according to claim 12 wherein R.sub.3 is ethyl.
- 14. A method according to claim 2 wherein the reaction of step (B) occurs in a solvent selected from the group consisting of an aprotic organic ether, aliphatic hydrocarbon, and an aromatic hydrocarbon.
- 15. A method according to claim 14 wherein said solvent is tert-butyl methyl ether.
- 16. A method according to claim 2 further comprising isolating said lithium compound of step (B) as a solid.
- 17. A method according to claim 2 wherein said reaction of step (B) occurs at about -80.degree. C. to about 50.degree. C.
- 18. A method according to claim 17 wherein said reaction occurs at about 40.degree. C. to about 50.degree. C.
- 19. A method according to claim 2 wherein said mixture of strong acids of step (C) comprises methanesulfonic acid and trifluoroacetic acid.
- 20. A method according to claim 2 wherein said electrophilic scavenger of step (C) is thioanisole.
- 21. A method according to claim 2 wherein said step (C) occurs at about 45.degree. C. to about reflux.
Parent Case Info
This application is a continuation application of International Patent Application No. PCT/US97/15729, filed Sep. 10, 1997, which, in turn, claims priority of U.S. Provisional Application No. 60/026,005, filed Sep. 12, 1996, now abandoned.
US Referenced Citations (2)
Number |
Name |
Date |
Kind |
4933470 |
Jones |
Jun 1990 |
|
5364862 |
Spada et al. |
Nov 1994 |
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Continuations (1)
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Number |
Date |
Country |
Parent |
PCTUS9715729 |
Sep 1997 |
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