Iodine → N-(6-chloro-3-iodopyridin-2-yl)pivalamide
Reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])[CH:5]=[CH:4][CH:3]=1.[Li]C(C)(C)C.CCCCCC.[I:26]I>C1COCC1>[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C:9](=[O:14])[C:10]([CH3:11])([CH3:13])[CH3:12])[C:5]([I:26])=[CH:4][CH:3]=1Participants
Procedure
To a solution of N-(6-chloropyridin-2-yl)-2,2-dimethylpropionamide (20 g, 94 mmol) in dry THF (500 mL) at −78° C., 1.3 M t-BuLi in hexane (220 mL, 282 mmol) is added dropwise. The reaction mixture is stirred for 30 min and a solution of iodine (29 g, 114 mmol) in dry THF is added. The reaction mixture is stirred for 3 h at −78° C. then is warmed to ambient temperature and stirred for another 1 h. The reaction mixture is quenched with 1N HCl and is extracted with ethyl acetate (2×250 mL). The organic layers are separated and washed with Na2S2O3 solution and saturated NaHCO3 solution, respectively. The combined organic layers are dried (Na2SO4) and evaporated under reduced pressure. The crude residue is purified by flash column chromatography using 20% EtOAc/petroleum ether to afford the title compound as a pale yellow solid (15 g, 49%).
Workup
- stirringThe reaction mixture is stirred for 3 h at −78° C.
- stirringstirred for another 1 h
- customThe reaction mixture is quenched with 1N HCl
- extractionis extracted with ethyl acetate (2×250 mL)
- customThe organic layers are separated
- washwashed with Na2S2O3 solution and saturated NaHCO3 solution
- dry with materialThe combined organic layers are dried (Na2SO4)
- customevaporated under reduced pressure
- customThe crude residue is purified by flash column chromatography
Sources & evidence
- ORD record
- ord-7d2da0b64d6a4a7a8023817a6cae65db
- Source dataset
- uspto-grants-2015_07
- Patent number
- US09073926B2
Reaction notes
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