Step 3:Preparation of intermediate 6
To a solution of NaH (0.35g, 14.8mmol, 2.0eq) in THF (37mL, c=0.4) was added 5 (0.75g, 8.8mmol, 1.2eq). To the solution was added4 (2.0g, 7.4mmol, 1.0eq) in THF (20mL, c=0.37). The reaction mixture was then stirred at room temperature overnight. To the suspension was added water (20mL) and EA (50mL). The organic phase was washed with water (50mL×2). Then the organic phase was adjusted to pH 2, extracted with EA(40mL×2). The aqueous fractions were combined and adjusted to pH 9, then extracted with EA (40×2). The combined organic fractions were washed with brine, dried over Na2SO4, filtered and concentrated under reduce pressure. The residue was washed with n-hexane to give the intermediate 6 (0.48g, yield=24%, HPLC: 99.3%) as a solid.