2,2,2-Trifluoroethanol → 5-Hydroxy-5-(2,2,2-trifluoro-ethoxymethyl)-2-(4-trifluoromethoxy-phenyl)-hexahydro-cyclopenta[c]pyrrol-1-one

HRID 1887500Notes

Reaction equation

[Na].[F:2][C:3]([F:7])([F:6])[CH2:4][OH:5].[F:8][C:9]([F:29])([F:28])[O:10][C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH2:21][CH:20]3[CH2:22][C:23]4([CH2:26][CH:19]3[C:18]2=[O:27])[CH2:25][O:24]4)=[CH:13][CH:12]=1>O>[OH:24][C:23]1([CH2:25][O:5][CH2:4][C:3]([F:7])([F:6])[F:2])[CH2:26][CH:19]2[C:18](=[O:27])[N:17]([C:14]3[CH:13]=[CH:12][C:11]([O:10][C:9]([F:8])([F:28])[F:29])=[CH:16][CH:15]=3)[CH2:21][CH:20]2[CH2:22]1

Participants

Conditions

Temperature: 80 °C

Procedure

A small piece of sodium was added to 2,2,2-Trifluoro-ethanol (20 mL), and the mixture was stirred at 80° C. for 5 minutes, then rac-(3aR,5S,6aS)-2-[4-(trifluoromethoxy)phenyl]hexahydro-1H-spiro[cyclopenta[c]pyrrole-5,2′-oxiran]-1-one was added. The mixture was stirred for 6 h. The solution was then poured into water (25 mL) and extracted with ether (3×20 mL), dried over Na2SO4. The solvent was removed and the residue was purified by prep-TLC (petroleum ether:ethyl acetate=1:1) to yield the title compound. 1H NMR (300 MHz, CDCl3): δ 7.66-7.63 (m, 2H), 7.20-7.17 (m, 2H), 4.13 (t, 1H, J=9.6 Hz), 3.86 (q, 2H, J=8.7 Hz), 3.71-3.61 (m, 3H), 3.22-3.17 (m, 1H), 3.05-2.99 (m, 1H), 2.38-2.33 (m, 1H), 2.09-1.76 (m, 4H); LC-MS: 414.1 [M+1]+.

Workup

stirringThe mixture was stirred for 6 h
extractionextracted with ether (3×20 mL)
dry with materialdried over Na2SO4
customThe solvent was removed
customthe residue was purified by prep-TLC (petroleum ether:ethyl acetate=1:1)

Sources & evidence

ORD record: ord-ec7be8b9e9684da5a31eeedaefbe8dbd
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08501768B2

Reaction notes

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