2-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl → 4-(Hydroxymethyl)-3-methylbenzonitrile

HRID 2410553Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][OH:9])=[C:4]([CH3:10])[CH:3]=1.COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.[CH3:40][N:41](C=O)C.O>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].[C-]#N.[Zn+2].[C-]#N>[OH:9][CH2:8][C:5]1[CH:6]=[CH:7][C:2]([C:40]#[N:41])=[CH:3][C:4]=1[CH3:10]

Participants

Conditions

Temperature: 130 °C

Procedure

A mixture of (4-bromo-2-methylphenyl)methanol (603 mg, 3.0 mmol), Pd2(dba)3 (110 mg, 0.12 mmol), S-Phos (99 mg, 0.24 mmol) and zinc cyanide (421 mg, 3.6 mmol) was prepared in a mixture of DMF/water (99:1, 5 mL) under nitrogen atmosphere and heated at 130° C. for 30 minutes under microwave irradiation. The suspension was filtered through a Celite pad and the filter-cake washed with EtOAc. The filtrate was washed with water and brine. The organic phase was passed through a hydrophobic frit and the solvent evaporated in vacuo. The residue was purified by flash chromatography (silica, petrol ether/EtOAc) to give the title compound. 1H NMR (CDCl3, 400 MHz) δ 7.58-7.48 (2H, m), 7.44 (1H, s), 4.75 (2H, d, J=5.5 Hz), 2.33 (3H, s), 1.85-1.78 (1H, m).

Workup

filtrationThe suspension was filtered through a Celite pad
washthe filter-cake washed with EtOAc
washThe filtrate was washed with water and brine
customthe solvent evaporated in vacuo
customThe residue was purified by flash chromatography (silica, petrol ether/EtOAc)

Sources & evidence

ORD record: ord-cc1c17d423004d0990c38fbb2a6cb07b
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08815919B2

Reaction notes

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