Methyl iodide → N-(6-ethyl-3-methyl-pyridin-2-yl)-2,2-dimethyl-propionamide
Reaction equation
[CH2:1]([C:3]1[N:8]=[C:7]([NH:9][C:10](=[O:15])[C:11]([CH3:14])([CH3:13])[CH3:12])[CH:6]=[CH:5][CH:4]=1)[CH3:2].[C:16]([Li])(C)(C)C.CI>C(OCC)C.O>[CH2:1]([C:3]1[N:8]=[C:7]([NH:9][C:10](=[O:15])[C:11]([CH3:14])([CH3:13])[CH3:12])[C:6]([CH3:16])=[CH:5][CH:4]=1)[CH3:2]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- -20 °C
Procedure
A solution of N-(6-ethyl-pyridin-2-yl)-2,2-dimethyl-propionamide (24.0 g, 0.116 mol) in diethyl ether (600 mL, 0.2 M) is cooled to −78° C. and treated with tert-butyllithium (144 mL 1.7 M in pentane). After the addition is complete the solution is warmed to −20° C. for 2 h, treated with a solution of methyliodide (23 mL, 0.372 mol) in diethylether (10 mL) and warmed to room temperature. After stirring overnight the reaction is diluted with water, extracted with diethyl ether and dried over MgSO4. The resulting solution is filtered through a short pad of silica gel, concentrated and recrystallized from heptane to give N-(6-ethyl-3-methyl-pyridin-2-yl)-2,2-dimethyl-propionamide (17.6 g, 69%) as an off-white crystalline solid. mp 72-75° C.; Rf 0.43 (50% ethyl acetate in hexanes); 1H NMR (DMSO-d6, 300 MHz) δ 9.48 (s, 1H), 7.53 (d, J=7.8 Hz, 1 H), 7.48 (d, J=7.5 Hz, 1 H), 2.65 (q, J=7.5 Hz, 2 H), 2.02 (s, 3 H), 1.20 (s, 9 H), 1.18 (t, J=7.5 Hz, 3 H); LRMS calcd for C13H20N2O: 220.3; found 220.0 (M)+. Anal. Calcd for C13H20N2O : C, 70.87; H, 9.15; N, 12.72. Found C, 70.70; H, 9.18; N, 12.74.
Workup
- additionAfter the addition
- temperaturewarmed to room temperature
- extractionextracted with diethyl ether
- dry with materialdried over MgSO4
- filtrationThe resulting solution is filtered through a short pad of silica gel
- concentrationconcentrated
- customrecrystallized from heptane
Sources & evidence
- ORD record
- ord-73aea3d4fa2c457dbd6fe1958143f382
- Source dataset
- uspto-grants-2008_04
- Patent number
- US07361671B2
Reaction notes
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