Claims
- 1. A process for the preparation of enalapril ##STR5## comprising reacting a dipeptide ##STR6## in ethanol, powdered sieves, one or more additives, an ethanol solution of catalyst, with an .alpha.-ketoester ##STR7## under hydrogen, while stirring, to produce the enalapril.
- 2. The process as recited in claim 1 wherein the catalyst is Ra-Ni, Pt/Al.sub.2 O.sub.3, and Pd/Al.sub.2 O.
- 3. The process as recited in claim 2 wherein the additives are selected from: amino acid derivatives, carbohydrates, salts, organic acids, and Lewis acids.
- 4. The process as recited in claim 3 wherein one of the additives is a salt selected from: LiF, NaF, KF, CsF, LiCl, NaCl, KCl, LiBr, NaBr, KBr, NaI, tetraalkylammonium bromides, wherein alkyl is defined as C.sub.1 -C.sub.6 alkyl.
- 5. The process as recited in claim 3 wherein one of the additives is an organic acid selected from: acetic acid, propionic acid, trifluoroacetic acid, citric acid, lactic acid, ascorbic acid, pyroglutamic acid, diphenylacetic acid, tartaric acid, indole-3-acetic acid, nicotinic acid, nipecotic acid, and picolinic acid.
- 6. The process as recited in claim 3 wherein two additives are used.
- 7. The process as recited in claim 6 wherein the catalyst is Ra-Ni.
- 8. The process as recited in claim 7 wherein the second additive is a salt.
- 9. The process as recited in claim 8 wherein the second additive is a salt selected from: LiF, NaF, KF, CsF, LiCl, NaCl, KCl, LiBr, NaBr, KBr, NaI, tetraalkylammonium bromides, wherein alkyl is defined as C.sub.1 -C.sub.6 alkyl.
- 10. The process as recited in claim 9 wherein the two additives are: acetic acid (HOAc) and potassium fluoride (KF), or acetic acid (HOAc) and cesium fluoride (CsF).
- 11. The process as recited in claim 10 wherein about 2 psia to about 100 psia of hydrogen is used.
- 12. The process as recited in claim 11 wherein the reaction temperature is about 0.degree. C. to about 40.degree. C.
- 13. The process as recited in claim 12 wherein about 2 psia to about 54 psia of hydrogen is used.
- 14. The process as recited in claim 13 wherein the reaction temperature is about 15.degree. C. to about 30.degree. C.
- 15. The process as recited in claim 6 wherein the catalyst is Pt/Al.sub.2 O.
- 16. The process as recited in claim 15 wherein the second additive is a salt.
- 17. The process as recited in claim 16 wherein the second additive is a salt selected from: LiF, NaF, KF, CsF, LiCl, NaCl, KCl, LiBr, NaBr, KBr, NaI, tetraalkylammonium bromides, wherein alkyl is defined as C.sub.1 -C.sub.6 alkyl.
- 18. The process as recited in claim 17 wherein the two additives are: acetic acid (HOAc) and sodium bromide (NaBr).
- 19. The process as recited in claim 18 wherein about 2 psia to about 100 psia of hydrogen is used.
- 20. The process as recited in claim 19 wherein the reaction temperature is about 0.degree. C. to about 40.degree. C.
- 21. The process as recited in claim 20 wherein about 2 psia to about 54 psia of hydrogen is used.
- 22. The process as recited in claim 21 wherein the reaction temperature is about 15.degree. C. to about 30.degree. C.
Parent Case Info
Provisional Appln No. 60/101,458 Sep. 23, 1998.
US Referenced Citations (7)
Non-Patent Literature Citations (1)
Entry |
Blacklock et al, "Synthesis of Semisynthetic Dipeptides Using N-Carboxyanhydrides and Chiral Induction on raney Nickel", J. Org. Chem., 1988, 53, 836-844. |