Methyl chloroformate → Methyl 5-bromo-3-cyanopyridin-2-ylcarbamate
Reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[NH2:11][C:12]1[C:17]([C:18]#[N:19])=[CH:16][C:15]([Br:20])=[CH:14][N:13]=1.Cl[C:22]([O:24][CH3:25])=[O:23]>C1COCC1>[Br:20][C:15]1[CH:16]=[C:17]([C:18]#[N:19])[C:12]([NH:11][C:22](=[O:23])[O:24][CH3:25])=[N:13][CH:14]=1Participants
Procedure
Lithium bis(trimethylsilyl)amide in THF (1.0 N, 22 mL, 22 mmol) was added to a stirred solution of 2-amino-5-bromopyridine-3-carbonitrile (2.0 g, 10 mmol) in THF (30 mL) at −78° C. and the mixture was stirred at this temperature for 30 minutes. Methyl chloroformate (1.06 g, 11.1 mmol) was added and the mixture was warmed to room temperature and stirred for 2 hours. It was cooled in ice bath and quenched with saturated aqueous ammonium chloride (50 mL). The aqueous layer was extracted with ethyl acetate (3×50 mL) and the combined organic fractions were washed with brine (2×50 mL), dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by LC (elution with 10% ethyl acetate in petroleum ether) to afford the carbamate (1.43 g, 63%). 1H NMR (400 MHz, CDCl3) δ 3.85 (s, 3H), 7.45 (br s, 1H), 8.05 (s, 1H), 8.65 (s, 1H). LCMS (M−1, 254.0).
Workup
- stirringstirred for 2 hours
- temperatureIt was cooled in ice bath
- customquenched with saturated aqueous ammonium chloride (50 mL)
- extractionThe aqueous layer was extracted with ethyl acetate (3×50 mL)
- washthe combined organic fractions were washed with brine (2×50 mL)
- dry with materialdried over anhydrous sodium sulfate
- concentrationconcentrated under vacuum
- customThe residue was purified by LC (elution with 10% ethyl acetate in petroleum ether)
Sources & evidence
- ORD record
- ord-e54832e03a9d413992ce3852e97aa1cf
- Source dataset
- uspto-grants-2015_11
- Patent number
- US09175010B2
Reaction notes
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