4-Methylmorpholine → (-)-methyl(S)-2-[(2-amino-3-nitrobenzoyl)amino]propanoate

Temperature

0 °C

To a stirred and cooled (−12° C.) mixture of 9.10 parts of 2-amino-3-nitrobenzoic acid, 6.95 parts of methyl L-α-alanine monohydrochloride, 13.50 parts of 1-hydroxy-1H-1,2,4-benzotriazole monohydrate and 178 parts of tetrahydrofuran there were added portionwise 5.05 parts of N-methylmorpholine and, after 5 min, 10.3 parts of N,N′-methanetetraylbis[cyclohexanamine] under an argon atmosphere. Stirring was continued for 5½ hours at −12° C. and for 15 hours at room temperature. After cooling to 0° C. for ½ hour, the reaction mixture was filtered and the filtrate was evaporated. The residue was partitioned between ethyl acetate and a saturated sodium hydrogen carbonate solution. The organic layer was separated, washed with NaHCO3 (sat.), dried, filtered and evaporated. The residue was triturated with hexane. The product was filtered off and dried, yielding 13.08 parts (97.9%) of (−)-methyl(S)-2-[(2-amino-3-nitrobenzoyl)amino]propanoate; mp. 132.9° C. (interm. 24).

1. temperaturecooled
2. stirringStirring
3. waitwas continued for 5½ hours at −12° C. and for 15 hours at room temperature
4. filtrationthe reaction mixture was filtered
5. customthe filtrate was evaporated
6. customThe residue was partitioned between ethyl acetate
7. customThe organic layer was separated
8. washwashed with NaHCO3 (sat.)
9. customdried
10. filtrationfiltered
11. customevaporated
12. customThe residue was triturated with hexane
13. filtrationThe product was filtered off
14. customdried

ORD record

ord-d68b7e8cda6c46e198e00ca9756e68a0

Source dataset

uspto-grants-2001_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06201119B1