Cyclohexanone → 1-(2-((Tert-butyldimethylsilyloxy)methyl)-4-(trifluoromethyl)phenyl)cyclohexanol

HRID 2075096Notes

Reaction equation

HRID 2075096 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([Li])CCC.[C:26]1(=[O:32])[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1>O1CCCC1>[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[C:26]1([OH:32])[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1)([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7]

Participants

5

Reactant 3

HCID 7967CyclohexanoneHCID 58968745(2-Bromo-5-(trifluoromethyl)benzyloxy)(tert-butyl)dimethylsilaneHCID 178418339Butyllithium

Product 1

HCID 589687241-(2-((Tert-butyldimethylsilyloxy)methyl)-4-(trifluoromethyl)phenyl)cyclohexanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of (2-bromo-5-(trifluoromethyl)benzyloxy)(tert-butyl)dimethylsilane (140 mg; 0.379 mmol) in tetrahydrofuran (0.5 mL) at −78° C. was added dropwise n-butyllithium (0.4 mL; 0.64 mmol; 1.6M in hexanes). The reaction was stirred at −78° C. for 15 minutes. Cyclohexanone (0.8 mL; 7.7 mmol) was added stirred at −78° C. for 10 minutes. The reaction was then stirred at room temperature for 15 minutes. The reaction was quenched with 2 drops of water. It was diluted with ethyl acetate and filtered through a column containing silica gel and sodium sulfate. The crude was then purified over a 12 g RediSep column (Teledyne Isco Inc., Lincoln Nebr.) (eluted with 10-40% ethyl acetate in heptane) to give 112 mg (76%) as a liquid. MS (ES+): Calc: 388.5, Found: 433.2 (M+HCO2−) 1H NMR (400 MHz, CDCl3) δ ppm 7.58 (s, 1H), 7.51 (d, J=8.30 Hz, 1H), 7.45 (d, J=8.30 Hz, 1H), 5.05 (s, 2H), 3.92 (s, 1H), 1.94-1.73 (m, 6H), 1.68-1.6 (m, 2H), 1.31 (m, 2H), 0.93 (s, 9H), 0.12 (s, 6H).

Workup

  1. stirringstirred at −78° C. for 10 minutes
  2. stirringThe reaction was then stirred at room temperature for 15 minutes
  3. customThe reaction was quenched with 2 drops of water
  4. additionIt was diluted with ethyl acetate
  5. filtrationfiltered through a column
  6. additioncontaining silica gel and sodium sulfate
  7. customThe crude was then purified over a 12 g RediSep column (Teledyne Isco Inc., Lincoln Nebr.) (eluted with 10-40% ethyl acetate in heptane)
  8. customto give 112 mg (76%) as a liquid

Sources & evidence

ORD record
ord-a92bddc1e66542cd9b21608ed51b5dbd
Source dataset
uspto-grants-2011_04
Patent number
US07919506B2

Reaction notes

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