[F:1][C:2]1([F:16])[CH2:5][CH:4]([C:6]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:7])[CH2:3]1.[CH2:17](I)[CH3:18].C[Si]([N-][Si](C)(C)C)(C)C.[K+]>C1COCC1>[CH2:17]([C:4]1([C:6]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:7])[CH2:3][C:2]([F:16])([F:1])[CH2:5]1)[CH3:18]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).
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