反応 #2286379

反応方程式

Iodomethane

Water

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

sodium hydride

→

desired product

収率 56.0%

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

収率 56.0%

溶媒

ethyl acetate

DMF

反応条件

後処理

1. 1
   workup.STIRRINGstirred for 5.5 h
2. 2
   その他the resulting biphasic mixture was separated
3. 3
   抽出the aqueous layer was extracted one time with ethyl acetate
4. 4
   洗浄The combined organic extracts were washed twice with brine
5. 5
   乾燥dried over MgSO4
6. 6
   ろ過filtered
7. 7
   濃縮concentrated to dryness under reduced pressure
8. 8
   その他The crude product was purified by silica gel column chromatography (0 to 100% ethyl acetate/hexanes)

実験手順

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).

出典