反应 #2286374

反应方程式

2,2,2-trifluoro-N-methyl-N-(2-pyridin-3-yl-thiazol-5-yl)-acetamide

N-chlorosuccinimide

N-chlorosuccinimide

→

desired product

N-(4-Chloro-2-pyridin-3-yl-thiazol-5-yl)-2,2,2-trifluoro-N-methyl-acetamide

溶剂

acetonitrile

反应条件

后处理

1. 1
   温度The reaction mixture was cooled to room temperature
2. 2
   温度heated to 35° C. under nitrogen for 2 h
3. 3
   温度The reaction mixture was cooled
4. 4
   浓缩concentrated under reduced pressure
5. 5
   workup.DISSOLUTIONThe residue was redissolved in dichloromethane (80 mL)
6. 6
   洗涤washed with water (70 mL)
7. 7
   萃取The aqueous layer was re-extracted with methylene chloride (100 mL)
8. 8
   洗涤The combined organic layers were washed with water (50 mL) and brine (50 mL)
9. 9
   干燥dried over sodium sulfate
10. 10
    过滤filtered
11. 11
    浓缩concentrated under reduced pressure
12. 12
    其他purified
13. 13
    洗涤The product eluted with a gradient of acetonitrile in water

实验过程

A suspension of 2,2,2-trifluoro-N-methyl-N-(2-pyridin-3-yl-thiazol-5-yl)-acetamide (1.0 g, 3.5 mmol) and N-chlorosuccinimide (0.557 g, 4.2 mmol) in acetonitrile (30 mL) was heated to 63° C. under nitrogen for 3 h. The reaction mixture was cooled to room temperature and it was treated with additional N-chlorosuccinimide (0.557 g, 4.2 mmol) and heated to 35° C. under nitrogen for 2 h. The reaction mixture was cooled and concentrated under reduced pressure. The residue was redissolved in dichloromethane (80 mL) and washed with water (70 mL). The aqueous layer was re-extracted with methylene chloride (100 mL). The combined organic layers were washed with water (50 mL) and brine (50 mL), dried over sodium sulfate, filtered, concentrated under reduced pressure and purified using reverse phase chromatography. The product eluted with a gradient of acetonitrile in water. The desired product was isolated as a thick brown gum (0.337 g, 30%): 1H NMR (400 MHz, CDCl3) δ 9.12 (br, 1H), 8.75 (br, 1H), 8.22 (d, J=7.9 Hz, 1H), 7.28 (br, 1H), 3.40 (s, 3H); 19F NMR (376 MHz, CDCl3) δ −69.3; ESIMS m/z 324.3 (M+2); IR (thin film) 1772 cm−1.

来源