Water → (2-(Cyclohexyl(methoxy)methyl)-5-(trifluoromethyl)benzyloxy)(tert-butyl)dimethylsilane

HRID 2075054Notes

Reaction equation

HRID 2075054 reaction equation
[Si:1]([O:8][CH2:9][C:10]1[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][C:11]=1[CH:20]([CH:22]1[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1)[OH:21])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].[Na+].[CH3:30]I.O>C1COCC1>[CH:22]1([CH:20]([O:21][CH3:30])[C:11]2[CH:12]=[CH:13][C:14]([C:16]([F:19])([F:18])[F:17])=[CH:15][C:10]=2[CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]1

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 58968683(2-((Tert-butyldimethylsilyloxy)methyl)-4-(trifluoromethyl)-phenyl)-(cyclohexyl)-methanol

Product 1

HCID 58968692(2-(Cyclohexyl(methoxy)methyl)-5-(trifluoromethyl)benzyloxy)(tert-butyl)dimethylsilaneYield 88%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (2-((tert-butyldimethylsilyloxy)methyl)-4-(trifluoromethyl)-phenyl)-(cyclohexyl)-methanol (1.25 g, 3.11 mmol) in THF (5 mL) at 0° C. was added sodium hydride (385 mg, 9.6 mmol). The mixture was stirred at room temperature for 1 hour, cooled to 0° C. and methyl iodide (1.0 mL, 16 mmol) was added. The mixture was stirred at room temperature overnight. Water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by chromatography over 25+S Biotage silica column (eluted with 0-5% ethyl acetate in heptane) to afford the title compound as a colorless oil (1.14 g, 88%). 1H NMR (400 MHz, CDCl3) δ ppm 0.12 (s, 6H) 0.94-0.96 (m, 9H) 0.98-1.29 (m, 6H) 1.54-1.59 (m, 1H) 1.61-1.67 (m, 2H) 1.71-1.79 (m, 1H) 2.00 (d, J=12.03 Hz, 1H) 3.13 (s, 3H) 4.08 (d, J=7.47 Hz, 1H) 4.71 (d, J=13.69 Hz, 1H) 4.85 (d, J=13.69 Hz, 1H) 7.44 (d, J=8.30 Hz, 1H) 7.52 (d, J=7.88 Hz, 1H) 7.76 (s, 1H).

Workup

  1. temperaturecooled to 0° C.
  2. stirringThe mixture was stirred at room temperature overnight
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by chromatography over 25+S Biotage silica column (eluted with 0-5% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-acfc753172bf49c686cba40a36f185dd
Source dataset
uspto-grants-2011_04
Patent number
US07919506B2

Reaction notes

Loading…