Hydrogen Cyanide → 6-Acetyl-4-chloro-3-(cyanomethyl)-3'-fluorobiphenyl-2-carbonitrile

HRID 1192590Notes

Reaction equation

[C-:1]#[N:2].[Na+].S(=O)(=O)(O)O.C#N.[C:11]([C:14]1[CH:15]=[C:16]([Cl:31])[C:17]([CH2:29]Br)=[C:18]([C:27]#[N:28])[C:19]=1[C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=1)(=[O:13])[CH3:12]>O.C(#N)C>[C:11]([C:14]1[CH:15]=[C:16]([Cl:31])[C:17]([CH2:29][C:1]#[N:2])=[C:18]([C:27]#[N:28])[C:19]=1[C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=1)(=[O:13])[CH3:12]

Participants

Conditions

Temperature: 60 °C

Procedure

To a mixture of sodium cyanide (562 mg, 11.5 mmol) in water (3 mL) was carefully added mixture of sulfuric acid (2.9 mL, 5.5 mmol) at 0° C. (the reaction generates hydrogen cyanide and must be run in a fume hood with good ventilation), followed by a solution of 6-acetyl-3-(bromomethyl)-4-chloro-3′-fluorobiphenyl-2-carbonitrile (414 mg, 1.13 mmol) in acetonitrile (10 mL). The reaction was heated at 60° C. for 1 hour with pH adjusting to 9 by the addition of solid sodium cyanide. The reaction was cooled and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate and then concentrated to dryness under reduced pressure. The residue was purified on silica gel, eluting with 0 to 40% ethyl acetate in hexane (146 mg, 41%). LCMS calculated for C17H11ClFN2O (M+H)+: m/z=313.1; Found: 313.1.

Workup

temperatureThe reaction was cooled
extractionextracted with ethyl acetate
washThe combined organic layers were washed with brine
dry with materialdried over sodium sulfate
concentrationconcentrated to dryness under reduced pressure
customThe residue was purified on silica gel
washeluting with 0 to 40% ethyl acetate in hexane (146 mg, 41%)

Sources & evidence

ORD record: ord-a5097ce202ff4a94a9b03359c734089b
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08680108B2

Reaction notes

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