Sodium borohydride → 3-(3,4-Dimethylphenyl)-2-(3-fluorophenyl)propanenitrile

HRID 879962Notes

Reaction equation

HRID 879962 reaction equation
[BH4-].[Na+].[CH3:3][C:4]1[CH:5]=[C:6](/[CH:11]=[C:12](\[C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=2)/[C:13]#[N:14])[CH:7]=[CH:8][C:9]=1[CH3:10]>CCO>[CH3:3][C:4]1[CH:5]=[C:6]([CH2:11][CH:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=2)[C:13]#[N:14])[CH:7]=[CH:8][C:9]=1[CH3:10]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 67775546(2E)-3-(3,4-dimethylphenyl)-2-(3-fluorophenyl)acrylonitrile

Product 1

HCID 677775573-(3,4-Dimethylphenyl)-2-(3-fluorophenyl)propanenitrileYield 100.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 3,4-dimethylbenzaldehyde (CAS 68844-97-3) (4.0 g, 29.6 mmol) and 3-fluoro-benzeneacetonitrile (CAS 501-00-8) (4.35 g, 29.6 mmol) in absolute EtOH, 30 mL, was added NaOMe (0.1 equiv), then the reaction mixture was stirred at room temperature for 2 h. The reaction mixture was cooled to 0° C. and filtered. The precipitate was washed with cold EtOH and gave (2E)-3-(3,4-dimethylphenyl)-2-(3-fluorophenyl)acrylonitrile as a white solid (6.20 g, 78%). NaBH4 (1.8 g, 47 mmol) was added slowly to a solution of (2E)-3-(3,4-dimethylphenyl)-2-(3-fluorophenyl)acrylonitrile (6.17 g, 23.5 mmol) in EtOH (100 mL) under argon. The mixture was stirred at 70° C. for 16 h. The solution was cooled to room temperature and quenched with water. The reaction mixture was diluted with 100 mL water and acidified with 6M HCl (aq.). After extraction with ether (3×100 mL), the combined organic layers were washed with water and brine, dried over MgSO4, filtered and concentrated and gave 3-(3,4-dimethylphenyl)-2-(3-fluorophenyl)propanenitrile as a white solid (6 g, 96%). DIBAL-H (1.0 M in toluene, 14 mL, 14 mmol) was added dropwise to a solution of 3-(3,4-dimethylphenyl)-2-(3-fluorophenyl)propanenitrile (2.93 g, 11.72 mmol) in Toluene (40 mL) at −78° C. under argon. The mixture was stirred at −78° C. to −20° C. for 3 h and then quenched by slow addition of saturated NH4Cl solution (2 mL) followed by Celite (2 g) at −20° C. The mixture was diluted with Et2O (50 mL), warmed slowly to room temperature, and stirred till all aluminum precipitated. The solid was filtered and washed with ether (3×50 mL), the combined organic layers were dried over MgSO4, filtered, concentrated and gave Intermediate 5 (2.34 g, 74%).

Workup

  1. temperatureThe solution was cooled to room temperature
  2. customquenched with water
  3. additionThe reaction mixture was diluted with 100 mL water
  4. extractionAfter extraction with ether (3×100 mL)
  5. washthe combined organic layers were washed with water and brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-693394f458cf45ccb4f2e53021fdac24
Source dataset
uspto-grants-2015_03
Patent number
US08993553B2

Reaction notes

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