Hydrochloric Acid → Methyl 3-(4-fluoro-2-hydroxyphenyl)-3-oxopropanoate

Temperature

-78 °C

A 1.0 M tetrahydrofuran solution of lithium bis(trimethylsilyl)amide (39.0 mL, 39.0 mmol) was stirred at −78° C. and treated over a 25 min period with a solution of 1-(4-fluoro-2-hydroxyphenyl)ethanone (2.00 g, 13.0 mmol) in 50 mL of tetrahydrofuran. The resulting solution was stirred at −78° C. for 1 h, and then at −15° C. for 2 h. After being cooled again to −78° C., the solution was treated with a solution of dimethyl carbonate (1.20 mL, 14.3 mmol) in tetrahydrofuran (5 mL). The resulting mixture was allowed to warm to rt where it stirred overnight. After this time, the mixture was poured over ice and then concentrated hydrochloric acid (10 mL) was added. The resulting mixture was extracted three times with dichloromethane. The combined organic phases were washed twice with water, dried over sodium sulfate and then concentrated under vacuum to yield a residue. The residue was purified by radial thin-layer chromatography (silica gel, 2-40% ethyl acetate-hexane) to provide methyl 3-(4-fluoro-2-hydroxyphenyl)-3-oxopropanoate as a white solid (1.76 g, 64%). 1H NMR (400 MHz, CDCl3) δ ppm 3.78 (s, 3 H) 3.98 (s, 2 H) 6.62-6.71 (m, 2 H) 7.69 (dd, J=8.9, 6.4 Hz, 1 H) 12.15 (d, J=1.5 Hz, 1 H). Mass spectrum m/z 213.14 (M+H)+.

1. waitat −15° C. for 2 h
2. temperatureAfter being cooled again to −78° C.
3. temperatureto warm to rt where it
4. stirringstirred overnight
5. additionAfter this time, the mixture was poured over ice
6. extractionThe resulting mixture was extracted three times with dichloromethane
7. washThe combined organic phases were washed twice with water
8. dry with materialdried over sodium sulfate
9. concentrationconcentrated under vacuum
10. customto yield a residue
11. customThe residue was purified by radial thin-layer chromatography (silica gel, 2-40% ethyl acetate-hexane)

ORD record

ord-c0fc18ea2a074a6ca0ddb7742c995e18

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08759390B2