反应详情

温度

-78 °C

To a solution of benzyl 3,3-difluorocyclobutanecarboxylate (500 mg, 2.210 mmol) and EtI (0.714 mL, 8.84 mmol) in THF (15 mL) at −78° C. under a N2 atmosphere was added a solution of KHMDS (8.84 mL, 4.42 mmol, 0.5 M in toluene). The resulting solution was stirred at −78° C. for 6 h. The reaction was then allowed to warm to RT and stirred overnight. The reaction mass was then quenched with a saturated aq. solution of NH4Cl and the aqueous layer was 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 (4 g REDISEP® column, eluting with 15% EtOAc in hexanes). Fractions containing the product were combined and evaporated to afford Intermediate 301A as a pale yellow liquid (200 mg, 35.6%). 1H NMR (300 MHz, chloroform-d) δ ppm 7.32-7.44 (m, 5H), 5.19 (s, 2H), 2.90-3.11 (m, 2H), 2.38-2.57 (m, 2H), 1.28 (dt, J=8.97, 7.03 Hz, 2H), 0.79-0.93 (m, 3H).

1. temperatureto warm to RT
2. stirringstirred overnight
3. customThe reaction mass was then quenched with a saturated aq. solution of NH4Cl
4. extractionthe aqueous layer was extracted with diethyl ether (3×25 mL) The combined organic fractions
5. washwere 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 (4 g REDISEP® column, eluting with 15% EtOAc in hexanes)
10. additionFractions containing the product
11. customevaporated