反应 #67729

反应方程式

triethylamine

5-methylpyridin-2-amine

1-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxylic acid

Thionyl chloride

→

product

收率 48.8%

1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(5-methylpyridin-2-yl)cyclopropanecarboxamide

收率 48.8%

溶剂

dichloromethane

N,N-dimethylformamide

反应条件

后处理

1. 1
   其他The excess thionyl chloride was removed under vacuum
2. 2
   workup.STIRRINGto stir for 15 hours at room temperature
3. 3
   洗涤The crude product was then washed two times with a 1M aqueous solution of hydrochloric acid, two times with a saturated aqueous solution of sodium bicarbonate, and finally two times with a saturated aqueous solution of sodium chloride
4. 4
   干燥The organic layer was dried over sodium sulfate
5. 5
   其他evaporated
6. 6
   其他purified on 120 g of silica gel utilizing a gradient of 0-30% ethyl acetate in hexanes

实验过程

1-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxylic acid (2.32 g, 9.58 mmol) was placed in an oven-dried flask under nitrogen. Thionyl chloride (3 mL) and N,N-dimethylformamide (0.3 mL) were added and the solution was allowed to stir for 30 minutes at room temperature. The excess thionyl chloride was removed under vacuum and the resulting solid was suspended in anhydrous dichloromethane (10 mL). This solution was then slowly added to a solution 5-methylpyridin-2-amine (0.798 g, 7.38 mmol) in anhydrous dichloromethane (10 mL) containing triethylamine (4.11 mL, 29.5 mmol). The resulting mixture was allowed to stir for 15 hours at room temperature. The crude product was then washed two times with a 1M aqueous solution of hydrochloric acid, two times with a saturated aqueous solution of sodium bicarbonate, and finally two times with a saturated aqueous solution of sodium chloride. The organic layer was dried over sodium sulfate, evaporated to near dryness, and then purified on 120 g of silica gel utilizing a gradient of 0-30% ethyl acetate in hexanes to yield the pure product (1.20 g, 3.60 mmol, 48.7%). ESI-MS m/z calc. 332.1. found 333.1 (M+1)+. Retention time 1.48 minutes.

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