Dichloromethane → 2-Chloro-4-(5-fluoro-4-hydroxymethyl-pyridin-3-yl)-benzonitrile
Reaction equation
[Cl:1][C:2]1[CH:9]=[C:8]([C:10]2[CH:11]=[N:12][CH:13]=[C:14]([F:18])[C:15]=2[CH:16]=[O:17])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[BH4-].[Na+].C(Cl)Cl>C1COCC1.O>[Cl:1][C:2]1[CH:9]=[C:8]([C:10]2[CH:11]=[N:12][CH:13]=[C:14]([F:18])[C:15]=2[CH2:16][OH:17])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Procedure
To the solution of 2-chloro-4-(5-fluoro-4-formylpyridin-3-yl)benzonitrile (45 mg, 0.17 mmol) in THF (3 mL) and water (1 mL) was added sodium borohydride (6.5 mg, 0.17 mmol) at 0° C. This reaction mixture was stirred for 0.5 h at room temperature. After addition of CH2Cl2, the organic layer was washed with saturated NaCl solution and extracted with DCM for five times. The combined extracts were dried over Na2SO4, filtered, and evaporated. The resulting mixture was passed through a pad of silica gel, rinsed with 0-50% EtOAc/heptane, and evaporated to give 2-Chloro-4-(5-fluoro-4-hydroxymethyl-pyridin-3-yl)-benzonitrile (21 mg, 46%) as a white solid. ESI-MS m/z: 263 [M+1]+, Retention time 1.11 min. 1H-NMR (CDCl3, 400 MHz) δ 4.56 (s, 2H), 7.66 (dd, J=8.4, 1.6 Hz, 1H), 7.88 (d, J=1.6 Hz, 1H), 7.93 (d, J=8.4 Hz, 1H), 8.39 (s, 1H), 8.55 (s, 1H).
Workup
- washthe organic layer was washed with saturated NaCl solution
- extractionextracted with DCM for five times
- dry with materialThe combined extracts were dried over Na2SO4
- filtrationfiltered
- customevaporated
- washrinsed with 0-50% EtOAc/heptane
- customevaporated
Sources & evidence
- ORD record
- ord-a72c8c6dea854f8daf063d4edb0352df
- Source dataset
- uspto-grants-2013_08
- Patent number
- US08519134B2
Reaction notes
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