Claims
- 1. A process for preparing a pyrrolidinone derivative of structure (1) ##STR11## in which R is hydrogen, comprising: (a) N-deprotecting a compound of structure (2) ##STR12## wherein R.sup.2 is benzyl, .alpha.-methylbenzyl or p-methoxybenzyl;
- R.sup.3 is hydrogen, and X is straight or branched alkyl containing 1 to 10 carbon atoms;
- to give a compound of structure (3) ##STR13## wherein X and R.sup.3 are as defined above; and (b) cyclizing the compound of structure (3) intramolecularly by heating at 0.degree. to 120.degree. C.
- 2. A process for preparing a pyrrolidinone derivative of structure (1) ##STR14## in which R is alkanoyl containing 1 to 10 carbon atoms, comprising: (a) N-deprotecting a compound of structure (2) ##STR15## wherein R.sup.2 is benzyl, .alpha.-methylbenzyl or p-methoxybenzyl;
- R.sup.3 is hydrogen; and X is straight or branched alkyl containing 1 to 10 carbon atoms;
- to give a compound of structure (3) ##STR16## wherein X and R.sup.3 are as defined above; (b) cyclizing the compound of structure (3) intramolecularly by heating at 0.degree. to 120.degree. C.; and
- (c) reacting the cyclized compound with an acyl halide or acid anhydride in which acyl is an alkanoyl containing 1 to 10 carbon atoms to yield a compound of structure (1).
- 3. A process for preparing a pyrrolidnone derivative of structure (1) ##STR17## in which R is straight or branched alkyl of 1 to 4 carbon atoms comprising:
- (a) N-deprotecting a compound of structure (2) ##STR18## wherein R.sup.2 is benzyl, .alpha.-methylbenzyl or p-methoxybenzyl;
- R.sup.3 is hydrogen; and X is straight or branched alkyl containing 1 to 10 carbon atoms;
- to give a compound of structure (3) ##STR19## wherein X and R.sup.3 are as defined above; (b) cyclizing the compound of structure (3) intramolecularly by heating at 0.degree. to 120.degree. C.; and
- (c) reacting the cyclized compound with an alkyl halide or sulfate in which the alkyl contains 1 to 4 carbon atoms to yield a compound of structure (1).
- 4. A process for preparing a pyrrolidinone derivative of structure (1) ##STR20## in which R is straight or branched alkyl of 1 to 4 carbon atoms comprising:
- (a) N-deprotecting a compound of structure (2) ##STR21## wherein R.sup.2 is benzyl, .alpha.-methylbenzyl or p-methoxybenzyl;
- R.sup.3 is straight or branched alkyl of 1 to 4 carbon atoms; and X is straight or branched alkyl
- containing 1 to 10 carbon atoms to give a compound of structure (3) ##STR22## wherein X and R.sup.3 are as defined above; and (b) cyclizing said compound of structure (3) intramolecularly by heating at 0.degree. to 120.degree. C.
- 5. The process of claim 1, 2, 3 or 4 wherein the compound of structure (2) is N-deprotected by catalytic hydrogenation.
- 6. The process of claim 1, 2, 3 or 4 wherein the compound of structure (2) is N-deprotected by treatment with a mixture of formic acid and methanol and palladium-on-charcoal.
- 7. A process for preparing a pyrrolidinone derivative of structure (1) ##STR23## in which R is hydrogen which comprises: (a) N-deprotecting and cyclizing intramolecularly by heating at 90.degree. to 160.degree. C. a compound of structure (2A) ##STR24## wherein R.sup.4 and R.sup.5 are independently hydrogen, alkyl containing 1 to 4 carbon atoms, phenyl, or R.sup.4 and R.sup.5 together are 1,4-butylene or 1,5-pentylene;
- R.sup.3 is hydrogen; and X is straight or branched alkyl of 1 to 10 carbon atoms;
- to give a compound of structure (1).
- 8. A process for preparing a pyrrolidinone derivative of structure (1) ##STR25## in which R is alkanoyl containing 1 to 10 carbon atoms, which comprises: (a) N-deprotecting and cyclizing intramolecularly by heating at 90.degree. to 160.degree. C. the compound of structure (2A) ##STR26## wherein R.sup.4 and R.sup.5 are independently hydrogen, alkyl containing 1 to 4 carbon atoms, phenyl, or R.sup.4 and R.sup.5 together are 1,4-butylene or 1,5-pentylene;
- R.sup.3 is hydrogen; and X is straight or branched alkyl of 1 to 10 carbon atoms; and
- (b) reacting the cyclized compound, with an acyl halide or acid anhydride in which acyl is alkanoyl containing 1 to 10 carbon atoms to give a compound (1).
- 9. A process for preparing a pyrrolidinone derivative of structure (1) ##STR27## in which R is straight or branched alkyl of 1 to 4 carbon atoms, which comprises:
- (a) N-deprotecting and cyclizing intramolecularly by heating at 90.degree. to 160.degree. C. the compound of structure (2A); ##STR28## wherein R.sup.4 and R.sup.5 are independently hydrogen, alkyl containing 1 to 4 carbon atoms, phenyl, or R.sup.4 and R.sup.5 together are 1,4-butylene or 1,5-pentylene;
- R.sup.3 is hydrogen; and X is straight or branched alkyl of 1 to 10 carbon atoms; and
- (b) reacting the cyclized compound, with an alkyl halide or sulfate in which alkyl is of 1 to 4 carbon atoms to give a compound (1).
- 10. A process for preparing a pyrrolidinone derivative of structure (1) ##STR29## in which R is straight or branched alkyl of 1 to 4 carbon atoms, which comprises:
- (a) N-deprotecting and cyclizing intramolecularly by heating at 90.degree. to 160.degree. C. the compound of structure (2A) ##STR30## wherein R.sup.4 and R.sup.5 are independently hydrogen, alkyl containing 1 to 4 carbon atoms, phenyl, or R.sup.4 and R.sup.5 together are 1,4-butylene or 1,5-pentylene;
- R.sup.3 is a straight or branched alkyl of 1 to 4 carbon atoms; and X is straight or branched alkyl of 1 to 10 carbon atoms.
- 11. A process according to claim 7, 8, 9, or 10 in which the N-deprotection is effected in the presence of acetic or benzoic acid.
- 12. A process according to claim 7, 8, 9 or 10 in which in the compound of structure (2A) R.sup.4 is hydrogen, R.sup.5 is an isopropyl group and R.sup.3 is hydrogen.
- 13. A process for preparing a pyrrolidinone derivative of structure (1) ##STR31## in which R is hydrogen, comprising: (a) reacting an alkyl 3,4-epoxybutanoate of structure (4) ##STR32## wherein X is alkyl of 1 to 10 carbon atoms with a glycinamide derivative of structure (5) ##STR33## wherein R.sup.2 is benzyl, .alpha.-methylbenzyl or p-methoxybenzyl to give a compound a structure (2) ##STR34## wherein X and R.sub.2 are as defined above, and R.sup.3 is R as defined above;
- (b) N-deprotecting the compound of structure (2) to give a compound of structure (3) ##STR35## wherein X and R.sup.3 are as defined above; (c) cyclizing the compound of structure (2) intramolecularly by heating at 0.degree. to 120.degree. C.
- 14. A process for preparing a pyrrolidinone derivative of structure (1) ##STR36## in which R is alkanoyl containing 1 to 10 carbon atoms, comprising: (a) reacting an alkyl 3,4-epoxybutanoate of structure (4) ##STR37## wherein X is alkyl of 1 to 10 carbon atoms with a glycinamide derivative of structure (5) ##STR38## wherein R.sup.2 is benzyl, .alpha.-methylbenzyl or p-methoxybenzyl to give a compound of structure (2) ##STR39## wherein X and R.sub.2 are as defined above, and R.sup.3 is hydrogen; (b) N-deprotecting the compound of structure (2) to give a compound of structure (3) ##STR40## wherein X and R.sup.3 are as defined above (c) cyclizing the compound of structure (3) intramolecularly by heating at 0.degree. to 120.degree. C.; and
- (d) reacting the cyclized compound with an acyl halide or acid anhydride in which acyl is alkanoyl containing 1 to 10 carbon atoms to give a compound (1).
- 15. A process for preparing a pyrrolidinone derivative of structure (1) ##STR41## in which R is straight or branched alkyl of 1 to 4 carbon atoms, comprising:
- (a) reacting an alkyl 3,4-epoxybutanoate of structure (4) ##STR42## wherein X is alkyl of 1 to 10 carbon atoms with a glycinamide derivative of structure (5) ##STR43## wherein R.sup.2 is benzyl, .alpha.-methylbenzyl or p-methoxybenzyl to give a compound of structure (2) ##STR44## wherein X and R.sub.2 are as defined above, and R.sup.3 is hydrogen; (b) N-deprotecting the compound of structure (2) to give a compound of structure (3) ##STR45## wherein X and R.sup.3 are as defined above; (c) cyclizing the compound of structure (3) intramolecularly by heating at 0.degree. to 120.degree. C.; and
- (d) reacting the cyclized compound with an alkyl halide or sulfate in which alkyl is of 1 to 4 carbon atoms to give a compound (1).
- 16. A process for preparing a pyrrolidinone derivative of structure (1) ##STR46## in which R is straight or branched alkyl of 1 to 4 carbon atoms, comprising:
- (a) reacting an alkyl 3,4-epoxybutanoate of structure (4) ##STR47## wherein X is alkyl of 1 to 10 carbon atoms with a glycinamide derivative of structure (5) ##STR48## wherein R.sup.2 is benzyl, .alpha.-methylbenzyl or p-methoxybenzyl to give a compound a structure (2) ##STR49## wherein X and R.sub.2 are as defined above, and R.sup.3 is hydrogen; (b) reacting said compound of structure (2) with an alkyl halide or sulfate to yield a compound of structure (2) in which R.sup.3 is straight or branched alkyl of 1 to 4 carbon atoms;
- (c) N-deprotecting said compound of structure (2) to give a compound of structure (3) ##STR50## wherein X and R.sup.3 are as defined above; and (d) cyclizing the compound of structure (3) intermolecularly by heating at 0.degree. to 120.degree. C.
- 17. The process of claim 13, 14, 15, or 16 wherein the compound of structure (2) is N-deprotected by catalytic hydrogenation.
- 18. The process of claim 13, 14, 15, or 16 wherein the compound of structure (2) is N-deprotected by treatment with a mixture of formic acid and methanol and palladium-on-charcoal.
- 19. A process for preparing a pyrrolidinone derivative of structure (1) ##STR51## in which R is hydrogen, comprising (a) reacting an alkyl 3,4-epoxybutanoate of structure (4) ##STR52## wherein X is alkyl of 1 to 10 carbon atoms with a glycinamide derivative of structure (5A) ##STR53## wherein R.sup.4 and R.sup.5 are independently hydrogen, alkyl containing 1 to 4 carbon atoms, phenyl, or R.sup.4 and R.sup.5 together are 1,4-butylene or 1,5-pentylene, to give a compound of structure (2A) ##STR54## wherein R.sup.4, R.sup.5 and X are as defined above, and R.sup.3 is R as defined above; and
- (b) deprotecting and cyclizing intermolecularly by heating in 90.degree. to 160.degree. C. the compound of structure (2A).
- 20. A process for preparing a pyrrolidinone derivative of structure (1) ##STR55## in which R is alkanoyl containing 1 to 10 carbon atoms, comprising: (a) reacting an alkyl 3,4-epoxybutanoate of structure (4) ##STR56## wherein X is alkyl of 1 to 10 carbon atoms with a glycinamide derivative of structure (5A) ##STR57## wherein R.sup.4 and R.sup.5 are independently hydrogen, alkyl containing 1 to 4 carbon atoms, phenyl, or R.sup.4 and R.sup.5 together are 1,4-butylene or 1,5-pentylene, to give a compound of structure (2A) ##STR58## wherein R.sup.4, R.sup.5 and X are as defined above, and R.sup.3 is hydrogen;
- (b) N-deprotecting and cyclizing intermolecularly by heating at 90.degree. to 160.degree. C. the compound of structure (2A); and
- (c) reacting the cyclized compound with an acyl halide or acid anhydride in which acyl is alkanoyl containing 1 to 10 carbon atoms to give a compound (1).
- 21. A process for preparing a pyrrolidinone derivative of structure (1) ##STR59## in which R is straight or branched alkyl of 1 to 4 carbon atoms comprising:
- (a) reacting an alkyl 3,4-epoxybutanoate of structure (4) ##STR60## wherein X is alkyl of 1 to 10 carbon atoms with a glycinamide derivative of structure (5A) ##STR61## wherein R.sup.4 and R.sup.5 are independently hydrogen, alkyl containing 1 to 4 carbon atoms, phenyl, or R.sup.4 and R.sup.5 together are 1,4-butylene or 1,5-pentylene, to give a compound of structure (2A) ##STR62## wherein R.sup.4, R.sup.5 and X are as defined above, and R.sup.3 is hydrogen;
- (b) N-deprotecting and cyclizing intermolecularly by heating at 90.degree. to 160.degree. C. the compound of structure (2A); and
- (c) reacting the cyclized compound with an alkyl halide or sulfate in which alkyl is of 1 to 4 carbon atoms to give a compound (1).
- 22. A process for preparing a pyrrolidinone derivative of structure (1) ##STR63## in which is straight or branched alkyl of 1 to 4 carbon atoms comprising: (a) reacting an alkyl 3,4-epoxybutanoate of structure (4) ##STR64## wherein X is alkyl of 1 to 10 carbon atoms with a glycinamide derivative of structure (5A) ##STR65## wherein R.sup.4 and R.sup.5 are independently hydrogen, alkyl containing 1 to 4 carbon atoms, phenyl, or R.sup.4 and R.sup.5 together are 1,4-butylene or 1,5-pentylene, to give a compound of structure (2A) ##STR66## wherein R.sup.4, R.sup.5 and X are as defined above, and R.sup.3 is hydrogen;
- (b) reacting said compound of structure (2A) with an alkyl halide or sulfate to yield a compound of structure (2A) in which R.sup.3 is a straight or branched alkyl of 1 to 4 carbon atoms;
- (c) N-deprotecting and cyclizing intermolecularly by heating at 90.degree. to 160.degree. C. the compound of structure (2A).
- 23. The process of claim 19, 20, 21 or 22 in which N-deprotection is effected in the presence of acetic or benzoic acid.
- 24. The process of claim 19, 20, 21 or 22 in which in the compound of structure (2A) R.sup.4 is hydrogen, R.sup.5 is an isopropyl group and R.sup.3 is hydrogen.
Priority Claims (1)
Number |
Date |
Country |
Kind |
19802 A/84 |
Feb 1984 |
ITX |
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Parent Case Info
This is a continuation of application Ser. No. 092,250, filed Sept. 2, 1987, which is a continuation of Ser. No. 705,818, filed Feb. 26, 1985, both now abandoned.
US Referenced Citations (4)
Number |
Name |
Date |
Kind |
4118396 |
Pifferi et al. |
Oct 1978 |
|
4124594 |
Monguzzi et al. |
Nov 1978 |
|
4173569 |
Banfi et al. |
Nov 1979 |
|
4476308 |
Aschwanden et al. |
Oct 1984 |
|
Foreign Referenced Citations (2)
Number |
Date |
Country |
1059137 |
Jul 1979 |
CAX |
57-183756 |
Nov 1982 |
JPX |
Non-Patent Literature Citations (2)
Entry |
Noller, Chemistry of Organic Compounds, 3rd Ed. (1965), pp. 813-814. |
Pifferi et al., Il Farmaco (Ed. Sc.) 32: 602-613 (1977). |
Continuations (2)
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Number |
Date |
Country |
Parent |
92250 |
Sep 1987 |
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Parent |
705818 |
Feb 1985 |
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