Water → HCID 59192648, compound

HRID 511933Notes

Reaction equation

HRID 511933 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:12]([C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)[C:13]#[N:14])[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[CH2:22](Br)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[OH-].[K+].O>C1(C)C=CC=CC=1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[F:1][C:2]1[CH:3]=[C:4]([C:12]([C:15]2[CH:16]=[CH:17][C:18]([F:21])=[CH:19][CH:20]=2)([CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:13]#[N:14])[CH:5]=[C:6]([C:8]([F:10])([F:11])[F:9])[CH:7]=1

Participants

7

Reactant 4

HCID 962WaterHCID 7498Benzyl BromideHCID 14797Potassium HydroxideHCID 59192793HCID 59192793, compound

Product 1

HCID 59192648HCID 59192648, compoundYield 59%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 1140TolueneSolvent

Procedure

To a solution of 2-(3-fluoro-5-(trifluoromethyl)phenyl)-2-(4-fluorophenyl)acetonitrile (200 mg, 0.67 mmol) in toluene (7 mL) was added tetrabutylammonium bromide (65 mg, 0.20 mmol) and benzyl bromide (0.095 mL, 0.80 mmol) followed by an aqueous solution of 50% KOH (2.2 mL). The reaction mixture was vigorously stirred for 5 min, then poured into H2O (20 mL) and extracted with diethyl ether (2×20 mL). The combined organic portions were dried over anhydrous MgSO4, filtered and concentrated under reduced pressure to yield a residue. The residue was crystallized from methanol to give 2-(3-fluoro-5-(trifluoromethyl)phenyl)-2-(4-fluorophenyl)-3-phenylpropanenitrile (153 mg, 59% yield) as a white solid. LCMS: RT=2.11 min [M+H] 388.3 (2 min Phenomenex Luna C18 column, 4.6×30 mm eluting with 10-90% MeOH/H2O over 2 minutes containing 0.1% TFA; 5 mL/min, monitoring at 220 nm); NMR: 400 MHz 1H (CDCl3) ppm 3.59 (d, J=12.75 Hz, 1 H), 3.65 (d, J=13.18 Hz, 1 H), 6.87 (d, J=7.03 Hz, 2 H), 7.08 (t, J=8.35 Hz, 2 H), 7.18-7.32 (m, 8 H).

Workup

  1. extractionextracted with diethyl ether (2×20 mL)
  2. dry with materialThe combined organic portions were dried over anhydrous MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customto yield a residue
  6. customThe residue was crystallized from methanol

Sources & evidence

ORD record
ord-36660212157640e38a99866afd8ba4df
Source dataset
uspto-grants-2015_08
Patent number
US09102599B2

Reaction notes

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