Methyl iodide → Ethyl 2-(4,4-difluorocyclohexyl)propanoate

To a solution of ethyl 2-(4,4-difluorocyclohexyl)acetate (0.500 g, 2.424 mmol) in THF (10 mL) was added LDA (2.424 mL, 4.85 mmol, 2M in THF) dropwise at −78° C. and the reaction mixture was stirred at the same temperature for 45 min. MeI (0.606 mL, 9.70 mmol) was then added at −78° C. and the reaction mixture was slowly warmed to RT and stirred for 12 h. The reaction mixture was quenched with a saturated aqueous solution of NH4Cl and extracted with EtOAc (2×25 mL). The combined organic layer was dried over Na2SO4, filtered and the filtrate concentrated. The crude product was purified by silica gel chromatography (12 g REDISEP® column, eluting with 5% EtOAc in hexane). Fractions containing the product were combined and evaporated to afford Intermediate 232A as a pale yellow liquid (0.27 g, 50%). 1H NMR (300 MHz, chloroform-d) δ ppm 4.22-4.08 (m, 1H), 2.32 (quin, J=7.1 Hz, 1H), 2.20-2.02 (m, 2H), 1.88-1.76 (m, 2H), 1.75-1.62 (m, 3H), 1.51-1.35 (m, 2H), 1.33-1.23 (m, 4H), 1.20-1.11 (m, 3H).

1. stirringstirred for 12 h
2. customThe reaction mixture was quenched with a saturated aqueous solution of NH4Cl
3. extractionextracted with EtOAc (2×25 mL)
4. dry with materialThe combined organic layer was dried over Na2SO4
5. filtrationfiltered
6. concentrationthe filtrate concentrated
7. customThe crude product was purified by silica gel chromatography (12 g REDISEP® column, eluting with 5% EtOAc in hexane)
8. additionFractions containing the product
9. customevaporated

ORD record

ord-1e0868870f10409094ba9ce3e45c37be

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09273058B2