反应详情

To a stirred mixture of 3-ethoxy-2,6-difluoro-phenol (4.26 g, 0.024 mol) and ethyl-2-butynoate (5.48 g, 0.049 mol) in tetrahydrofuran (30 mL) was added 1,8-diazabicyclo[5.4.0]undec-7-ene (3.73 g, 0.025 mol) slowly. After addition was complete the mixture was stirred at reflux for 6 h. Upon completion of the reaction the tetrahydrofuran was removed in vacuo and the residue was diluted in diethyl ether and washed first with 1N aqueous hydrochloric acid, then 10% aqueous sodium hydroxide solution, a saturated sodium chloride solution and dried over magnesium sulfate. The crude product was purified by ISCO column chromatography (Teledyne Isco RediSep Flash Column 120 g, 0% to 20% ethyl acetate/hexanes) which afforded (E)-3-(3-ethoxy-2,6-difluoro-phenoxy)-but-2-enoic acid ethyl ester (4.63 g, 66%) as a white crystalline solid.

1. additionAfter addition
2. temperatureat reflux for 6 h
3. customwas removed in vacuo
4. additionthe residue was diluted in diethyl ether
5. washwashed first with 1N aqueous hydrochloric acid
6. dry with material10% aqueous sodium hydroxide solution, a saturated sodium chloride solution and dried over magnesium sulfate
7. customThe crude product was purified by ISCO column chromatography (Teledyne Isco RediSep Flash Column 120 g, 0% to 20% ethyl acetate/hexanes) which