Ammonium Chloride → 2-(2-Hydroxypropan-2-yl)isonicotinonitrile
Reaction equation
[C:1]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][N:11]=1)[C:7]#[N:8])(=[O:3])[CH3:2].[CH3:12][Mg]Br.[Cl-].[NH4+]>O1CCCC1.C1(C)C=CC=CC=1.O1CCCC1>[OH:3][C:1]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][N:11]=1)[C:7]#[N:8])([CH3:12])[CH3:2]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- -40 °C
Procedure
To a solution of 2-acetylisonicotinonitrile (67.1 g, 0.457 mol) in tetrahydrofuran (2400 mL) was added dropwise a solution of methylmagnesium bromide (3.0 M, 167.6 mL, 0.503 mol) in toluene/tetrahydrofuran mixture (3:1) at −40° C. over a period of 2.5 h. The reaction mixture was stirred at −40° C. for another 2 h. A saturated aqueous solution of ammonium chloride (50 mL) was added. The resulting mixture was warmed to room temperature and another 400 mL of a saturated aqueous solution of ammonium chloride was added. The layers were separated and the aqueous layer was extracted with dichloromethane (400 mL×2). The combined organics were dried over sodium carbonate and sodium sulfate and concentrated. The residue was purified via flash chromatography (ethyl acetate/petroleum ether 1:20, 0.3% triethylamine) to afford 2-(2-hydroxypropan-2-yl)isonicotinonitrile (33.0 g, 44.3%).
Workup
- temperatureThe resulting mixture was warmed to room temperature
- customThe layers were separated
- extractionthe aqueous layer was extracted with dichloromethane (400 mL×2)
- dry with materialThe combined organics were dried over sodium carbonate and sodium sulfate
- concentrationconcentrated
- customThe residue was purified via flash chromatography (ethyl acetate/petroleum ether 1:20, 0.3% triethylamine)
Sources & evidence
- ORD record
- ord-add0479f7f5542198bbe3d6ff2c574ff
- Source dataset
- uspto-grants-2016_03
- Patent number
- US09296745B2
Reaction notes
Loading…