反応 #67725

反応方程式

O,N-dimethyl hydroxylamine hydrochloride

6-chloro-nicotinic acid

N-methyl morpholine

NaHCO3

iso-butyl chloroformate

→

6-chloro-N-methoxy-N-methyl-nicotinamide

収率 46.6%

溶媒

dichloromethane

反応条件

後処理

1. 1
   workup.STIRRINGThe mixture was stirred for 30 min at −25° C.
2. 2
   workup.STIRRINGThe mixture was stirred for an additional hour at room temperature
3. 3
   抽出The separated aqueous layer was extracted with dichloromethane (500 mL×3)
4. 4
   洗浄The combined organic layers were washed with water and brine
5. 5
   その他The solvent was evaporated
6. 6
   その他to give the crude product, which
7. 7
   その他was purified by column chromatography

実験手順

To a solution of 6-chloro-nicotinic acid (94.5 g, 0.6 mol) in dichloromethane (1000 mL) was added N-methyl morpholine (181.8 g, 1.8 mol) followed by iso-butyl chloroformate (81.9 g, 0.6 mol) at −25° C. under 1\2 atmosphere. The mixture was stirred for 15 minutes and then O,N-dimethyl hydroxylamine hydrochloride (64.35 g, 0.66 mol) was added. The mixture was stirred for 30 min at −25° C. and warmed to room temperature slowly. The mixture was stirred for an additional hour at room temperature and a saturated solution of NaHCO3 (800 mL) was added. The separated aqueous layer was extracted with dichloromethane (500 mL×3). The combined organic layers were washed with water and brine. The solvent was evaporated to give the crude product, which was purified by column chromatography to give the pure product 6-chloro-N-methoxy-N-methyl-nicotinamide as a white solid (56 g, 46.6%).

出典