Sodium hydride → 4-(3,5-Bis(trifluoromethyl)benzyloxy)-3-phenylbutanenitrile

HRID 349712Notes

Reaction equation

HRID 349712 reaction equation
[C:1]([CH2:3][CH:4]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:5]([O:7][CH3:8])=O)#[N:2].[Li+].[BH4-].[F:17][C:18]([F:32])([F:31])[C:19]1[CH:20]=[C:21]([CH:24]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:26]=1)CBr.[H-].[Na+]>C1COCC1.CN(C=O)C>[F:17][C:18]([F:31])([F:32])[C:19]1[CH:20]=[C:21]([CH:24]=[C:25]([C:27]([F:28])([F:29])[F:30])[CH:26]=1)[CH2:8][O:7][CH2:5][CH:4]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH2:3][C:1]#[N:2]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 1225733,5-Bis(trifluoromethyl)benzyl bromideHCID 4148881Lithium borohydrideHCID 18464584Methyl 3-cyano-2-phenylpropanoate

Product 1

HCID 866027574-(3,5-Bis(trifluoromethyl)benzyloxy)-3-phenylbutanenitrileYield 55%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

Methyl 3-cyano-2-phenylpropanoate (350 mg, 1.90 mmol) was treated with LiBH4 (2.28 mmol) in THF (20 ml) at 50° C. for 2 hours until completion of the reaction. It was quenched with water and extracted with ethyl acetate. The organic phase was washed with water, brine and dried with Na2SO4 before being concentrated to dryness. The crude product was then mixed with 3,5-bis(trifluoromethyl)benzyl bromide in DMF (20 ml) and sodium hydride (91 mg, 2.28 mmol) was added. The reaction mixture was stirred at room temperature for 30 minutes and quenched with water, and extracted with ethyl acetate. The organic phase was washed with water, brine and concentrated. The crude residue was purified by silica flash chromatography (15% ethyl acetate in hexanes) to afford the desired product (405 mg, 55% in two steps). 1H NMR (500 MHz, CDCl3) δ ppm 2.78 (dd, J=116.79, 7.32 Hz, 1 H) 2.88 (m, 1 H) 3.33 (m, 1 H) 3.81 (m, 2 H) 4.65 (s, 2 H) 7.27 (m, 2 H) 7.31 (m, 1 H) 7.37 (m, 2 H) 7.73 (s, 2 H) 7.80 (s, 1 H).

Workup

  1. customIt was quenched with water
  2. extractionextracted with ethyl acetate
  3. washThe organic phase was washed with water, brine
  4. dry with materialdried with Na2SO4
  5. concentrationbefore being concentrated to dryness
  6. additionwas added
  7. customquenched with water
  8. extractionextracted with ethyl acetate
  9. washThe organic phase was washed with water, brine
  10. concentrationconcentrated
  11. customThe crude residue was purified by silica flash chromatography (15% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-0ef09c58181743c3ac63cd465813d4cb
Source dataset
uspto-grants-2007_02
Patent number
US07179926B2

Reaction notes

Loading…