Hydrochloric Acid → (R)-2-Difluoromethoxymethyl-2-methyl-but-3-enoic acid

Temperature

5 °C

A solution of (R)-2-difluoromethoxymethyl-2-methyl-but-3-enoic acid methyl ester (159 mg, 0.8 mmol) in tetrahydrofuran (6 mL) was stirred at 5° C. under nitrogen. A solution of lithium hydroxide monohydrate (100 mg, 2.4 mmol) in water (1.5 mL) was added and the reaction mixture was stirred at 5° C. for 1 h and then at room temperature for 20 h. Water was added and the mixture was acidified to pH 2 with hydrochloric acid (2 M) and the mixture was extracted with diethyl ether. The organic extracts were combined and washed with brine. The organic solution was filtered through a hydrophobic frit and the filtrate was evaporated to afford the title compound (133 mg, 92%) as a clear oil. 1H NMR (300 MHz, d6-DMSO) 61.24 (s, 3H), 3.80 (d, J=9.4 Hz, 1H), 4.02 (d, J=9.4 Hz, 1H), 5.19 (dd, J=10.6 Hz, 1H), 5.20 (d, J=17.6 Hz, 1H), 5.91 (dd, J=17.6, 10.6 Hz, 1H), 6.68 (t, J=75.6 Hz, 1H), 12.5-13.0 (br s, 1H). LCMS (m/z) 179.1 [M−H], Tr=1.79 min.

1. waitat room temperature for 20 h
2. extractionthe mixture was extracted with diethyl ether
3. washwashed with brine
4. filtrationThe organic solution was filtered through a hydrophobic frit
5. customthe filtrate was evaporated

ORD record

ord-4bdfda19fa9c45a0a89e2ea44c87f52b

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09062092B2