Potassium Carbonate → 3'-(Cyanomethyl)-5-fluoro-2-methylbiphenyl-4-carbonitrile

HRID 75521

Reaction equation

Br[C:2]1[C:9]([CH3:10])=[CH:8][C:5]([C:6]#[N:7])=[C:4]([F:11])[CH:3]=1.C([O-])([O-])=O.[K+].[K+].[C:18]([CH2:20][C:21]1[CH:22]=[C:23](B(O)O)[CH:24]=[CH:25][CH:26]=1)#[N:19]>CN(C)C=O.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:18]([CH2:20][C:21]1[CH:26]=[C:25]([C:2]2[CH:3]=[C:4]([F:11])[C:5]([C:6]#[N:7])=[CH:8][C:9]=2[CH3:10])[CH:24]=[CH:23][CH:22]=1)#[N:19]

Participants

Conditions

Temperature: 150 °C

Procedure

Tetrakis(triphenylphosphine)palladium (10 mg, 0.1 mmol) was added into the solution of 4-bromo-2-fluoro-5-methylbenzonitrile (110 mg, 0.5 mmol), K2CO3 70% aqueous solution (1 mL) and 3-(cyanomethyl)phenylboronic acid (96 mg, 0.6 mmol) in 10 ml N,N-dimethyl formamide, the solution was heated at 150° C. under microwave condition for 20 minutes, and the reaction mixture was partitioned with 20 mL water and 50 mL ethyl acetate, the aqueous layer was extracted with ethyl acetate (100 mL×2), and the combined organic layer was washed by saturated solution of sodium bicarbonate, sodium chloride, and dried by sodium sulfate, and concentrated by give quantitative products 3′-(cyanomethyl)-5-fluoro-2-methylbiphenyl-4-carbonitrile 3 (114 mg, 88% yield, confirmed by LCMS: 251.10) without purification for next steps.

Workup

customthe reaction mixture was partitioned with 20 mL water and 50 mL ethyl acetate
extractionthe aqueous layer was extracted with ethyl acetate (100 mL×2)
washthe combined organic layer was washed by saturated solution of sodium bicarbonate, sodium chloride
dry with materialdried by sodium sulfate
concentrationconcentrated

Sources & evidence

ORD record: ord-1de5a6f96c6c4dc4916563c43b261c6e
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08835445B2

Linked notes

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