HCID 89634608, compound → (βS,3R)-3-(Fluoromethyl)-β-methyl-1-pyrrolidineethanol

A mixture of (R)-3-(fluoromethyl)-1-((S)-1-(trityloxy)propan-2-yl)pyrrolidine (19.0 g, 47.1 mmol) and formic acid/diethyl ether (4:1, 189 mL) was stirred at room temperature for 8 h. This reaction mixture was concentrated on a rotary evaporator. The residue was dissolved in DCM, washed with sat'd aqueous K2CO3, and washed with brine. Organic layer was dried over Na2SO4, filtered, and concentrated to give the crude product that was purified by silica gel chromatography (10:7 ethyl acetate/hexanes to 10:7:2:1 ethyl acetate/hexane/methanol/triethylamine) to afford (S)-2-((R)-3-(fluoromethyl)pyrrolidin-1-yl)propan-1-ol (3.9 g) as a dark orange oil. 1H NMR (400 MHz, DMSO-d6) δ 4.38-4.32 (m, 2H), 4.22-4.20 (m, 1H), 3.49-3.44 (m, 1H), 3.21-3.16 (m, 1H), 2.65-2.61 (m, 1H), 2.58-2.53 (m, 1H), 2.52-2.47 (m, 1H), 2.45-2.35 (m, 1H), 2.34-2.30 (m, 1H), 2.29-2.24 (m, 1H), 1.83-1.75 (m, 1H), 1.38-1.30 (m, 1H), 0.98 (d, 3H).

1. concentrationThis reaction mixture was concentrated on a rotary evaporator
2. dissolutionThe residue was dissolved in DCM
3. washwashed with sat'd aqueous K2CO3
4. washwashed with brine
5. dry with materialOrganic layer was dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customto give the crude product that
9. customwas purified by silica gel chromatography (10:7 ethyl acetate/hexanes to 10:7:2:1 ethyl acetate/hexane/methanol/triethylamine)

ORD record

ord-ddfe9fe75f6747718c1f185aa1e690a0

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09193714B2