4-Chloro-3-(trifluoromethyl)benzyl alcohol → 4-(Hydroxymethyl)-2-(trifluoromethyl)benzonitrile

HRID 2040567Notes

Reaction equation

Cl[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][OH:9])=[CH:4][C:3]=1[C:10]([F:13])([F:12])[F:11].[C:14]([Zn]C#N)#[N:15]>CC(N(C)C)=O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[OH:9][CH2:8][C:5]1[CH:6]=[CH:7][C:2]([C:14]#[N:15])=[C:3]([C:10]([F:13])([F:12])[F:11])[CH:4]=1

Participants

Conditions

Temperature: 150 °C

Procedure

To a solution of (4-chloro-3-(trifluoromethyl)phenyl)methanol (0.300 g, 1.425 mmol) in DMA was added dicyanozinc (0.335 g, 2.85 mmol) and tetrakis(triphenylphosphine) palladium (0) (0.165 g, 0.142 mmol). The reaction flask was degassed and charged with nitrogen, then heated at 150° C. for 6 h under microwave irradiation. The reaction mixture was poured into water and extracted with EtOAc. The EtOAc extract was washed with brine, dried over MgSO4 and purified by silica gel column chromatography to give the title compound as a white solid (0.105 g). LCMS m/z=202.1 [M+H]+. 1H NMR (400 MHz, CDCl3) δ ppm 1.98 (bs, 1H), 4.87 (s, 2H), 7.69 (d, J=0.88 Hz, 1H), 7.77-7.88 (m, 2H)

Workup

customThe reaction flask was degassed
additioncharged with nitrogen
additionThe reaction mixture was poured into water
extractionextracted with EtOAc
extractionThe EtOAc extract
washwas washed with brine
dry with materialdried over MgSO4
custompurified by silica gel column chromatography

Sources & evidence

ORD record: ord-ad09cf72b41641aca9864755aa4075a8
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08580841B2

Reaction notes

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