2-Bromoethanol → (R)-2-(3-(Fluoromethyl)pyrrolidin-1-yl)ethanol

Temperature

80 °C

A mixture of (R)-3-(fluoromethyl)pyrrolidine hydrochloride (Intermediate 8, 4.26 g, 30.6 mmol), 2-bromoethanol (4.35 mL, 61.3 mmol), and potassium carbonate (12.7 g, 92 mmol) in acetonitrile (120 mL) was heated at 80° C. overnight. After cooling, solids were filtered off and washed with acetonitrile. The filtrate was concentrated on a rotary evaporator to give a residue that was purified by silica gel chromatography eluting with 10:7 ethyl acetate/hexanes to 10:7:2:1 ethyl acetate/hexane/methanol/triethylamine to afford 2.9 g of (R)-2-(3-(fluoromethyl)pyrrolidin-1-yl)ethanol as a clear oil. 1H NMR (400 MHz, DMSO-d6) δ 4.44 (t, 1H), 4.34 (dd, 1H), 4.22 (dd, 1H), 3.44 (q, 2H), 2.58-2.51 (m, 1H), 2.48-2.38 (m, 5H), 2.32-2.28 (m, 1H), 1.85-1.74 (m, 1H), 1.39-1.31 (m, 1H).

1. temperatureAfter cooling
2. filtrationsolids were filtered off
3. washwashed with acetonitrile
4. concentrationThe filtrate was concentrated on a rotary evaporator
5. customto give a residue that
6. customwas purified by silica gel chromatography
7. washeluting with 10:7 ethyl acetate/hexanes to 10:7:2:1 ethyl acetate/hexane/methanol/triethylamine

ORD record

ord-77e6788e6a2044aeb4880d30a3814838

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09193714B2