Dimethylformamide → 3-(Hydroxymethyl)-5-(trifluoromethyl)benzonitrile
Reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:12][OH:13])[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[CH3:14][N:15](C=O)C>[C-]#N.[Zn+2].[C-]#N.[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:13][CH2:12][C:4]1[CH:3]=[C:2]([CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=1)[C:14]#[N:15]Participants
5
Reactant 2
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 160 °C
Procedure
A mixture of (3-bromo-5-trifluoromethyl-phenyl)-methanol (500 mg, 1.96 mmol), zinc cyanide (230 mg, 1.96 mmol) and tetrakis(triphenylphosphine) palladium (68 mg, 0.059 mmol) in DMF (2 ml) was heated by microwave at 160° C. for 20 minutes. The mixture was partitioned between ethyl ether (20 ml) and water (10 ml). The aqueous layer was extracted with ether and combined organic layers were washed with brine, dried (MgSO4) and concentrated in vacuo. The product was purified on Biotage column (12+M), eluting with 2% ethyl acetate in heptane (1 CV), 2-20% (10 CV), 20% (2CV) to yield the title compound (240 mg, 61%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ ppm 2.05 (s, 1H) 4.8 (s, 2H) 7.82 (s, 1H) 7.86 (s, 2H).
Workup
- customThe mixture was partitioned between ethyl ether (20 ml) and water (10 ml)
- extractionThe aqueous layer was extracted with ether
- washwere washed with brine
- dry with materialdried (MgSO4)
- concentrationconcentrated in vacuo
- customThe product was purified on Biotage column (12+M)
- washeluting with 2% ethyl acetate in heptane (1 CV), 2-20% (10 CV), 20% (2CV)
Sources & evidence
- ORD record
- ord-6a70a433f57740e1866c1daf659414a7
- Source dataset
- uspto-grants-2011_04
- Patent number
- US07919506B2
Reaction notes
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