Cyclohexanecarboxaldehyde → (2-((Tert-butyldimethylsilyloxy)methyl)-4-(trifluoromethyl)-phenyl)-(cyclohexyl)-methanol

HRID 2075053Notes

Reaction equation

HRID 2075053 reaction equation
Br[C:2]1[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][C:3]=1[CH2:4][O:5][Si:6]([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7].C([Mg]Cl)(C)C.[Li+].[Cl-].[CH:28]1([CH:34]=[O:35])[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1>C1COCC1>[Si:6]([O:5][CH2:4][C:3]1[CH:13]=[C:14]([C:17]([F:20])([F:19])[F:18])[CH:15]=[CH:16][C:2]=1[CH:34]([CH:28]1[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1)[OH:35])([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7]

Participants

5

Reactant 3

HCID 16275CyclohexanecarboxaldehydeHCID 58968745(2-Bromo-5-(trifluoromethyl)benzyloxy)(tert-butyl)dimethylsilaneHCID 178461733HCID 178461733, compound

Product 1

HCID 58968683(2-((Tert-butyldimethylsilyloxy)methyl)-4-(trifluoromethyl)-phenyl)-(cyclohexyl)-methanolYield 90.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of (2-bromo-5-(trifluoromethyl)benzyloxy)(tert-butyl)dimethylsilane (1.3 g, 3.5 mmol) in THF at 0° C. was added i-PrMgCl/LiCl in THF (3.5 mL, 4.5 mmol). The mixture was stirred at 0° C. for 4 hours and cyclohexanecarboxaldehyde (0.61 g, 0.65 mL, 5.4 mmol) was added. The mixture was stirred at 0° C.-room temperature for 1 hour, quenched with saturated aqueous ammonium chloride and extracted with ethyl acetate. Combined organic layers were washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by chromatography over 25+M Biotage silica column (eluted with 0-20% ethyl acetate in heptane) to afford the title compound (1.27 g, 90%). 1H NMR (400 MHz, CDCl13) δ ppm 0.13 (s, 6H) 0.94 (s, 9H) 0.96-1.38 (m, 7H) 1.63-1.73 (m, 2H) 1.77-1.83 (m, 1H) 2.06(d, J=13.28 Hz, 1H) 2.28 (d, J=3.73 Hz, 1H) 4.58 (dd, J=7.68, 3.94 Hz, 1H) 4.75 (d, J=13.28 Hz, 1H) 4.85 (d, J=13.28 Hz, 1H) 7.53 (s, 2H) 7.68 (s, 1H).

Workup

  1. stirringThe mixture was stirred at 0° C.-room temperature for 1 hour
  2. customquenched with saturated aqueous ammonium chloride
  3. extractionextracted with ethyl acetate
  4. washCombined organic layers were washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by chromatography over 25+M Biotage silica column (eluted with 0-20% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-17fdc32ea8ba49fdaf989bc7e80a2133
Source dataset
uspto-grants-2011_04
Patent number
US07919506B2

Reaction notes

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