反应详情

温度

50 °C

In a 25 mL round-bottom flask, (2S)-1,1,1-trifluoro-3-(2-(6-(trifluoromethyl)pyridin-3-yl)morpholino)propan-2-ol (384 mg, 1.12 mmol) was combined with dichloromethane (12 ml) to give a colorless solution. TEA (113 mg, 155 μl, 1.12 mmol) was added. 1-chloro-2-fluoro-4-isocyanatobenzene (211 mg, 1.23 mmol) was added. The reaction mixture was warmed at 50° C. overnight. Reaction was complete by LCMS. Two major close-running spots of similar intensity could be seen by TLC (silica 25% EtOAc in hexanes eluent), a front-running spot and a later-running spot. The crude material was purified by flash chromatography (silica gel, 80 g, 5% to 20% EtOAc in hexanes). Mixed fractions were purified by flash chromatography (silica gel, 80 g, 5% to 20% EtOAc in hexanes). Fractions from both columns that contained pure later-running product were concentrated, dissolved in ether and treated with 1M HCl in ether to form the HCl salt. The resultant salt formed a gummy solid, which was scraped on the sides of the flask to form an off-white solid. This solid was filtered and washed with ether. A portion of the product was lost during the transfer. The resultant solid was placed on the pump to afford (4-chloro-3-fluorophenyl)-carbamic acid (S)-2,2,2-trifluoro-1-[(S)-2-(6-trifluoromethyl-pyridin-3-yl)-morpholin-4-ylmethyl]-ethyl ester hydrochloride (60 mg) as an off-white solid. (M+H)+=516 m/e.

1. customto give a colorless solution
2. customReaction
3. customTwo major close-running spots of similar intensity
4. customThe crude material was purified by flash chromatography (silica gel, 80 g, 5% to 20% EtOAc in hexanes)
5. customMixed fractions were purified by flash chromatography (silica gel, 80 g, 5% to 20% EtOAc in hexanes)
6. concentrationwere concentrated
7. dissolutiondissolved in ether
8. additiontreated with 1M HCl in ether