تفاعل #2286379

معادلة التفاعل

Iodomethane

Water

(2-pyridin-3-yl-4-trifluoromethyl-thiazol-5-yl)-carbamic acid tert-butyl ester

sodium hydride

→

desired product

المردود 56.0%

methyl-(2-pyridin-3-yl-4-trifluoromethyl-thiazol-5-yl)carbamic acid tert-butyl ester

المردود 56.0%

المذيبات

ethyl acetate

DMF

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGstirred for 5.5 h
2. 2
   أخرىthe resulting biphasic mixture was separated
3. 3
   استخلاصthe aqueous layer was extracted one time with ethyl acetate
4. 4
   غسيلThe combined organic extracts were washed twice with brine
5. 5
   تجفيفdried over MgSO4
6. 6
   ترشيحfiltered
7. 7
   تركيزconcentrated to dryness under reduced pressure
8. 8
   أخرىThe crude product was purified by silica gel column chromatography (0 to 100% ethyl acetate/hexanes)

الإجراء التجريبي

To a solution of (2-pyridin-3-yl-4-trifluoromethyl-thiazol-5-yl)-carbamic acid tert-butyl ester (4.7 g, 13.6 mmol) in DMF (70 mL) at 0° C. was added sodium hydride (NaH, 0.65 g, 16.3 mmol, 60% dispersion in mineral oil) in one portion and the mixture was stirred for 50 min. Iodomethane (0.89 mL, 14.3 mmol) was added in one portion, and after 5 min the reaction mixture was warmed to room temperature and stirred for 5.5 h. Water and ethyl acetate were added, the resulting biphasic mixture was separated and the aqueous layer was extracted one time with ethyl acetate. The combined organic extracts were washed twice with brine, dried over MgSO4, filtered and concentrated to dryness under reduced pressure. The crude product was purified by silica gel column chromatography (0 to 100% ethyl acetate/hexanes) to give the desired product as a clear orange oil (2.72 g, 56%); IR (KBr) 3428, 2981, 1728, 1561 cm−1; 1H NMR (300 MHz, CDCl3) δ 9.11 (d, J=2.5 Hz, 1H), 8.72 (dd, J=4.9, 1.1 Hz, 1H), 8.26 (dt, J=8.0, 1.7 Hz, 1H), 7.42 (dd, J=8.0, 4.9 Hz, 1H), 3.28 (s, 3H), 1.45 (s, 9H); ESIMS m/z 360.6 (M+1).

المصدر