Water → HCID 59192648, compound

HRID 1952402Notes

Reaction equation

HRID 1952402 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-bc12f93b6b0d4c7792e4a649a7ada1c5
Source dataset
uspto-grants-2013_03
Patent number
US08404896B2

Reaction notes

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