Sodium hydride → 3-Trifluoromethyl-4-(2-(S)-butoxy)benzonitrile

HRID 1820963Notes

Reaction equation

HRID 1820963 reaction equation
F[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[C:10]([F:13])([F:12])[F:11].[CH3:14][C@H:15]([OH:18])[CH2:16][CH3:17].[H-].[Na+]>C1COCC1>[F:11][C:10]([F:13])([F:12])[C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:2]=1[O:18][C@H:15]([CH2:16][CH3:17])[CH3:14])[C:6]#[N:7]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1442554-Fluoro-3-(trifluoromethyl)benzonitrileHCID 444683(+)-2-Butanol

Product 1

HCID 184469513-Trifluoromethyl-4-(2-(S)-butoxy)benzonitrileYield 38.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1.1 g (5.9 mmol) of 4-fluoro-3-trifluoromethylbenzonitrile and 485 mg (6.5 mmol) of (S)-(+)-2-butanol in 10 mL of THF at −10° C. was treated with 235 mg (5.9 mmol) of sodium hydride. The resulting mixture was stirred cold for 2 h, then quenched with 10 mL of H2O. The quenched solution was extracted with 30 mL of Et2O, dried over MgSO4 and concentrated. Chromatography on a Biotage 40M cartridge using 4:1 v/v hexanes/Ethyl acetate as the eluant afforded 550 mg of the title compound: 1H NMR (500 MHz) δ 0.99 (t, J=7.6, 3H), 1.35 (d, J=6.2, 3H), 1.58-1.83 (m, 2H), 4.51 (septet, 1H), 7.04 (d, J=8.7, 1H), 7.75 (d, J=8.7, 1H), 7.85 (s, 1H).

Workup

  1. customquenched with 10 mL of H2O
  2. extractionThe quenched solution was extracted with 30 mL of Et2O
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-321e1b8a456648e9834a6dc3d6f27e86
Source dataset
uspto-grants-2009_10
Patent number
US07605171B2

Reaction notes

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