Sulfuric Acid → Dimethyl (3,3-difluoro-2-oxoheptyl)phosphonate

Temperature

-78 °C

A solution of dimethyl methylphosphonoate (6.5 g, 80 mmol, 2.2 equiv) in tetrahydrofuran (100 mL) was cooled to −78° C. and n-butyllithium (2.5 M in hexanes, 14 mL, 36 mmol, 1 equiv) was added dropwise. The solution was stirred at −78° C. for 30 min and ethyl 2,2-difluorohexanoate (6.5 g, 36 mmol, 1 equiv) was added dropwise. The solution was stirred at −78° C. for 1 h and warmed to 0° C. over 1 h. Pentane (100 mL) was added followed by the dropwise addition of 2M H2SO4 to pH=6. The aqueous layer was separated and extracted with pentane (3×15 mL). The organics were combined, dried over sodium sulfate, filtered, and concentrated to dryness under vacuum on a rotary evaporator. The crude oil was purified by column chromatography using methyl tert-butyl ether as eluant to afford 4.1 g of 26 as a yellow oil (44%).

1. stirringThe solution was stirred at −78° C. for 1 h
2. temperaturewarmed to 0° C. over 1 h
3. customThe aqueous layer was separated
4. extractionextracted with pentane (3×15 mL)
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated to dryness under vacuum on a rotary evaporator
8. customThe crude oil was purified by column chromatography

ORD record

ord-5e49633d997d4f62b4de16338cca4132

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08309744B2