Methyl iodide → HCID 118062254, compound

Temperature

-78 °C

To a solution of benzyl 3,3-difluorocyclobutanecarboxylate (2 g, 8.84 mmol) and MeI (2.202 mL, 35.4 mmol), in THF (15 mL) at −78° C. under a N2 atmosphere was added a solution of KHMDS (35.4 mL, 17.68 mmol, 0.5 M in toluene). The reaction mixture was then stirred at −78° C. for 6 h after which it was allowed to warm to RT and stir overnight. The reaction mass was then quenched with a saturated aq. solution of NH4Cl and extracted with diethyl ether (3×25 mL). The combined organic fractions were washed with water, dried over Na2SO4, filtered and concentrated under vacuum. The crude product was purified by silica gel chromatography (40 g REDISEP® column, eluting with 20% EtOAc in hexanes). Fractions containing the product were combined and evaporated to afford the Intermediate 296A as a pale yellow liquid (1.2 g, 56.5%). 1H NMR (400 MHz, chloroform-d) δ ppm 7.50-7.23 (m, 5H), 5.17 (s, 2H), 3.22-2.97 (m, 2H), 2.60-2.28 (m, 2H), 1.51 (s, 3H).

1. temperatureto warm to RT
2. stirringstir overnight
3. customThe reaction mass was then quenched with a saturated aq. solution of NH4Cl
4. extractionextracted with diethyl ether (3×25 mL)
5. washThe combined organic fractions were washed with water
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated under vacuum
9. customThe crude product was purified by silica gel chromatography (40 g REDISEP® column, eluting with 20% EtOAc in hexanes)
10. additionFractions containing the product
11. customevaporated

ORD record

ord-1faf1039ac954204be9ca8dcaccc5efd

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09273058B2