تفاعل #2286374

معادلة التفاعل

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

المذيبات

acetonitrile

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةThe reaction mixture was cooled to room temperature
2. 2
   درجة الحرارةheated to 35° C. under nitrogen for 2 h
3. 3
   درجة الحرارةThe reaction mixture was cooled
4. 4
   تركيزconcentrated under reduced pressure
5. 5
   workup.DISSOLUTIONThe residue was redissolved in dichloromethane (80 mL)
6. 6
   غسيلwashed with water (70 mL)
7. 7
   استخلاصThe aqueous layer was re-extracted with methylene chloride (100 mL)
8. 8
   غسيلThe combined organic layers were washed with water (50 mL) and brine (50 mL)
9. 9
   تجفيفdried over sodium sulfate
10. 10
    ترشيحfiltered
11. 11
    تركيزconcentrated under reduced pressure
12. 12
    أخرىpurified
13. 13
    غسيلThe product eluted with a gradient of acetonitrile in water

الإجراء التجريبي

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.

المصدر