Ethyl 2-butynoate → 3-(3-Chloro-2-fluoro-phenoxy)-but-2-enoic acid ethyl ester

Temperature

130 °C

A mixture of 3-chloro-2-fluoro-phenol (1.31 g, 8.93 mmol) and ethyl-2-butynoate (2.0 g, 17.83 mmol) in tetrahydrofuran (14 mL) was treated with 1,8-diazabicyclo[5.4.0]undec-7-ene (1.4 mL, 9.37 mmol). The reaction was then heated at 130° C. for 2 h. At this time, the reaction was cooled to 25° C. and was stirred at 25° C. overnight. At this time, the reaction was concentrated in vacuo. The residue was dissolved in dichloromethane (100 mL) and was washed with a 2N aqueous hydrochloric acid solution (1×100 mL), a 1N aqueous sodium hydroxide solution (1×100 mL) and a saturated aqueous sodium chloride solution (1×100 mL). The organics were then dried over magnesium sulfate, filtered, rinsed with dichloromethane, and concentrated in vacuo. Purification by Analogix flash chromatography (40 g, 1-10% ethyl acetate/hexanes) afforded 3-(3-chloro-2-fluoro-phenoxy)-but-2-enoic acid ethyl ester (1.41 g, 61%) as a white solid: HR-ES-MS m/z calculated for C12H12O3FCl [M+H]+ 259.0532, observed 259.0531; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.14 (t, J=7.1 Hz, 3H), 2.45 (s, 3H), 4.03 (q, J=7.1 Hz, 2H), 4.76 (s, 1H), 7.27-7.39 (m, 2H), 7.50-7.61 (m, 1H).

1. temperatureAt this time, the reaction was cooled to 25° C.
2. concentrationAt this time, the reaction was concentrated in vacuo
3. dissolutionThe residue was dissolved in dichloromethane (100 mL)
4. washwas washed with a 2N aqueous hydrochloric acid solution (1×100 mL)
5. dry with materialThe organics were then dried over magnesium sulfate
6. filtrationfiltered
7. washrinsed with dichloromethane
8. concentrationconcentrated in vacuo
9. customPurification by Analogix flash chromatography (40 g, 1-10% ethyl acetate/hexanes)

ORD record

ord-f140279614be41ee925f4348262a5f88

Source dataset

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07741327B2