Tetrabutylammonium Fluoride → (2-(Cyclopentyl(methoxy)methyl)-5-(trifluoromethyl)phenyl)methanol

To a solution of (2-(cyclopentyl(methoxy)methyl)-5-(trifluoromethyl)benzyloxy)(tert-butyl)-dimethylsilane (120 mg, 0.298 mmol) in THF at room temperature was added TBAF in THF (1.0M, 0.45 mL, 0.45 mmol). The mixture was stirred at room temperature overnight. Solvent was removed and the residue was purified by chromatography over 12+S Biotage silica column (eluted with 0-20% ethyl acetate in hexane) to afford the title compound as a colorless oil (70 mg, 81%). 1H NMR (400 MHz, CDCl3) δ ppm 1.05-1.16 (m, 1H) 1.23-1.35 (m, 1H) 1.38-1.69 (m, 5H) 1.81-1.91 (m, 1H) 2.19-2.33 (m, 1H) 2.92-2.99 (m, 1H) 3.17 (s, 3H) 4.21 (d, J=8.71 Hz, 1H) 4.80 (s, 2H) 7.47 (d, J=7.88 Hz, 1H) 7.54 (d, J=7.88 Hz, 1H) 7.69 (s, 1H). The racemic mixture was separated by chiral chromatography using preparative HPLC (Column: ChiralPak AD; Dimension: 5 cm×50 cm; Mobile phase: 98/2 heptane/ethanol, Flow rate: 120 mL/minutes). The expected preparative retention times for the two enantiomers were 15 minutes (Enantiomer 1) and 20 minutes (Enantiomer 2). Enantiomer 1: 1H NMR (400 MHz, CDCl3) δ ppm 1.05-1.17 (m, 1H) 1.26-1.37 (m, 1H) 1.42-1.72 (m, 5H) 1.83-1.92 (m, 1H) 2.23-2.33 (m, 1H) 2.38-2.47 (m, 1H) 3.18 (s, 3H) 4.20 (d, J=8.30 Hz, 1H) 4.82 (d, J=3.73 Hz, 2H) 7.47 (d, J=8.30 Hz, 1H) 7.55 (d, J=7.88 Hz, 1H) 7.69 (s, 1H). Enantiomer 2: 1H NMR (400 MHz, CDCl3) δ ppm 1.05-1.17 (m, 1H) 1.28-1.36 (m, 1H) 1.42-1.71 (m, 5H) 1.81-1.93 (m, 1H) 2.22-2.35 (m, 1H) 2.36-2.48 (m, 1H) 3.18 (s, 3H) 4.20 (d, J=8.71 Hz, 1H) 4.82 (d, J=3.73 Hz, 2H) 7.47 (d, J=8.30 Hz, 1H) 7.55 (d, J=8.30 Hz, 1H) 7.69 (s, 1H).

1. customSolvent was removed
2. customthe residue was purified by chromatography over 12+S Biotage silica column (eluted with 0-20% ethyl acetate in hexane)

ORD record

ord-7dfcb9cf1257426cab889c8ae2823345

Source dataset

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07919506B2