Water → (R)-2-Difluoromethoxymethyl-2-methyl-but-3-enoic acid methyl ester

A solution of (R)-2-hydroxymethyl-2-methyl-but-3-enoic acid methyl ester (288 mg, 2.0 mmol) in acetonitrile (8 mL) was stirred at room temperature under nitrogen. Copper(I) iodide (80 mg, 0.4 mmol) was added followed by difluoro-fluorosulfonyl-acetic acid (356 mg, 0.2 mL, 2.0 mmol) and the reaction mixture was heated at reflux for 30 minutes. The reaction mixture was cooled to room temperature, water was added and the mixture was extracted with ethyl acetate. The organic extracts were combined and washed with brine. The organic solution was filtered through a hydrophobic frit and the filtrate was evaporated. The residue was purified by silica gel chromatography using a gradient of pentane/diethyl ether 10:1 to 5:1 to afford the title compound (195 mg, 50%) as a clear oil. 1H NMR (300 MHz, CDCl3) δ 1.40 (s, 3H), 3.75 (s, 3H), 3.86 (d, J=9.4 Hz, 1H), 4.10 (d, J=9.4 Hz, 1H), 5.24 (d, J=17.4 Hz, 1H), 5.24 (dd, J=10.9 Hz, 1H), 5.95 (dd, J=17.4, 10.9 Hz, 1H), 6.22 (t, J=74.3 Hz, 1H).

1. temperaturethe reaction mixture was heated
2. temperatureat reflux for 30 minutes
3. extractionthe mixture was extracted with ethyl acetate
4. washwashed with brine
5. filtrationThe organic solution was filtered through a hydrophobic frit
6. customthe filtrate was evaporated
7. customThe residue was purified by silica gel chromatography

ORD record

ord-2300ff87636a4d93bacb3443e6c8deae

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09062092B2