Cyclopentanone → Ethyl 3-(cyclopentylamino)-2,2-difluoropropanoate

To a round bottom flask was added Ethyl 3-amino-2,2-difluoropropanoate (1.31 g, 4.9 mmol), THF (50 mL), cyclopentanone (0.46 mL, 5.1 mmol), and NaOAc (400 mg, 4.9 mmol). To this mixture was added sodium triacetoxyborohydride (1.6 g, 7.3 mmol) portionwise over 15 minutes. The reaction was left to stir overnight. It was then added slowly to a stirring solution of ice (30 mL), NaHCO3 (sat., 10 mL), and EtOAc (100 mL) cooled in an ice-salt bath. The layers were then separated and the aqueous pH further adjusted to 11 using 25% NaOH while cooling in the bath. The aqueous layer was washed with EtOAc (2×50 mL), the organic extracts combined, washed with cold NaHCO3, (sat. 20 mL×2) brine (20 mL), dried over MgSO4, filtered and concentrated to yield the desired product as a clear syrup (960 mg, 89%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.25 (t, J=7.07 Hz, 2H) 1.34-1.74 (m, 8H) 3.00 (q, 1H) 3.11 (t, J=14.15 Hz, 2H) 4.27 (q, J=7.07 Hz, 2H). [M+H] calc'd for C10H17F2NO2, 222. found 222.

1. waitThe reaction was left
2. temperaturecooled in an ice-salt bath
3. customThe layers were then separated
4. temperaturewhile cooling in the bath
5. washThe aqueous layer was washed with EtOAc (2×50 mL)
6. washwashed with cold NaHCO3, (sat. 20 mL×2) brine (20 mL)
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated

ORD record

ord-59c6c32dbdbb442d89d5b49af7ff741d

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08026234B2