Toluene → 5-(3,5-Difluorobenzyl)-2-fluorobenzonitrile

HRID 2068770Notes

Reaction equation

[C:1]([C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][C:8]=1[F:9])#[N:2].P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(C)C=CC=CC=1.[F:28][C:29]1[CH:30]=[C:31]([CH:34]=[C:35]([F:37])[CH:36]=1)[CH2:32]Br>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(OCC)C>[F:28][C:29]1[CH:30]=[C:31]([CH:34]=[C:35]([F:37])[CH:36]=1)[CH2:32][C:5]1[CH:6]=[CH:7][C:8]([F:9])=[C:3]([CH:4]=1)[C:1]#[N:2]

Participants

Conditions

Temperature: 100 °C

Procedure

3-Cyano-4-fluorophenylboronic acid (1.649 g, 10 mmol), powdered potassium phosphate (4.254 g, 20 mmol) and Pd(PPh3)4 (231 mg, 0.2 mmol) were charged in an oven-dried flask under argon atmosphere. The flask was evacuated and back-filled with argon thrice and then toluene (30 mL) and 3,5-difluorobenzyl bromide (1.295 mL, 10 mmol) were added by means of a syringe through a lattice stopper, under good stirring. The reaction mixture was heated to 100° C. in half an hour and maintained at that temperature for 1.5 hours. The black mixture was taken up with diethylether (200 mL), washed with saturated aqueous ammonium chloride (2×20 mL), brine (3×30 mL), dried over sodium sulphate and evaporated to dryness to afford 3.21 g of yellow oil. The crude was purified by flash chromatography on silica gel eluting with n-hexane/ethyl acetate 95:5 to yield 1.89 g (yield 76.4%) of whitish solid.

Workup

customThe flask was evacuated
additionback-filled with argon thrice
temperaturemaintained at that temperature for 1.5 hours
washwashed with saturated aqueous ammonium chloride (2×20 mL), brine (3×30 mL)
dry with materialdried over sodium sulphate
customevaporated to dryness

Sources & evidence

ORD record: ord-cd506a722532477885b3f6e4c424682c
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08299057B2

Reaction notes

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