Methyl iodide → HCID 59402251, compound

Temperature

0 °C

To a suspension of 60% dispersion of sodium hydride in mineral oil (1.5 g, 37.5 mmol) in anhydrous DMF (20 mL) cooled on an ice-bath to 0° C. was added dropwise a solution of (S)-benzyl 3-(tert-butoxycarbonylamino)pyrrolidine-1-carboxylate (10 g, 31.2 mmol) in anhydrous DMF (100 mL). The resulting mixture was stirred at 0° C. for 1 hour then at ambient temperature for 2 hours. The mixture was subsequently cooled to 0° C. and treated dropwise with iodomethane (2.1 mL, 34.3 mmol), and the mixture stirred at 0° C. for 1 hour then warmed to ambient temperature and stirred for 18 hours. The reaction mixture was diluted with water (300 mL) and the mixture extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried (MgSO4), filtered and concentrated under reduced pressure. The residual oil was purified by column chromatography (Biotage, 65M; 10-20% ethyl acetate:hexanes) to afford (S)-benzyl 3-(tert-butoxycarbonyl(methyl)amino)pyrrolidine-1-carboxylate (7.2 g, 69%).

1. waitat ambient temperature for 2 hours
2. temperatureThe mixture was subsequently cooled to 0° C.
3. stirringthe mixture stirred at 0° C. for 1 hour
4. temperaturethen warmed to ambient temperature
5. stirringstirred for 18 hours
6. extractionthe mixture extracted with ethyl acetate
7. washThe combined organic layers were washed with water and brine
8. dry with materialdried (MgSO4)
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customThe residual oil was purified by column chromatography (Biotage, 65M; 10-20% ethyl acetate:hexanes)

ORD record

ord-dd6c1e6c641a4a21afc0c2fbb14d4e0a

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08889704B2