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

HRID 2075034노트

반응식

HRID 2075034 반응식
[CH:1]1([CH:6]([O:26][CH3:27])[C:7]2[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][C:8]=2[CH2:9][O:10][Si](C(C)(C)C)(C)C)[CH2:5][CH2:4][CH2:3][CH2:2]1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[CH:1]1([CH:6]([O:26][CH3:27])[C:7]2[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][C:8]=2[CH2:9][OH:10])[CH2:5][CH2:4][CH2:3][CH2:2]1

참가 물질

4

반응물 2

HCID 2724141Tetrabutylammonium FluorideHCID 58968676(2-(Cyclopentyl(methoxy)methyl)-5-(trifluoromethyl)benzyloxy)(tert-butyl)dimethylsilane

생성물 1

HCID 58968669(2-(Cyclopentyl(methoxy)methyl)-5-(trifluoromethyl)phenyl)methanol수율 81.5%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-7dfcb9cf1257426cab889c8ae2823345
출처 데이터셋
uspto-grants-2011_04
특허 번호
US07919506B2

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