4-Methylmorpholine → HCID 22847908, compound

Temperature

-5 °C

N-(tert-Butoxycarbonyl)-L-alanine (12.8 g) was dissolved in methylene chloride (50 mL) and the solution cooled to -5° C., and treated with N-methylmorpholine (6.7 g). The resulting mixture was stirred and cooled to -5° to -10° C. and a cold (-5° C.) solution of isobutyl chloroformate (8.5 g) in methylene chloride (100 mL) added slowly while keeping the temperature at or below -5° C. The mixture was stirred for another 30 minutes at -5° to -10° C. To this mixture was then added a cold (0° C.) solution of (S)-3-amino-1-benzylpyrrolidine (10.0 g) in methylene chloride (100 mL) while keeping the temperature between 0° and -10° C. The reaction mixture was stirred at 0° to -5° C. for 1 hour and then at 15° to 25° C. for 2 hours. The mixture was treated with 300 mL of demineralized water and the layers separated. The organic phase was extracted with a solution of sodium bicarbonate (18.5 g) in demineralized water (200 mL) followed by demineralized water (300 mL). The organic phase was dried over sodium sulfate (50 g) and the product solution concentrated under vacuum to give 1-benzyl-3-(S)-[2-(S)-(tert-butoxycarbonylamino)propionylamino]pyrrolidine (21.3 g) as an off-white solid (mp: 102°-105° C.) which was used in the next step without further purification.

1. temperaturecooled to -5° to -10° C.
2. custombelow -5° C
3. stirringThe mixture was stirred for another 30 minutes at -5° to -10° C
4. customthe temperature between 0° and -10° C
5. stirringThe reaction mixture was stirred at 0° to -5° C. for 1 hour
6. customthe layers separated
7. extractionThe organic phase was extracted with a solution of sodium bicarbonate (18.5 g) in demineralized water (200 mL)
8. dry with materialThe organic phase was dried over sodium sulfate (50 g)
9. concentrationthe product solution concentrated under vacuum

ORD record

ord-3c8ddd40148a40ddae88e16a2a421e96

Source dataset

uspto-grants-1993_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05250704