Oxazole, 2-(2,6-difluorophenyl)-4,5-dihydro-4-(4-iodophenyl)- → 2-(2,6-Difluorophenyl)-4,5-dihydro-4-[4'-[[tris(1-methylethyl)silyl]thio][1,1'-biphenyl]-4-yl]oxazole

Participants

Reaction Steps

The title compound of Step A (4.3 g) was dissolved in 15 mL of THF under a nitrogen atmosphere and the reaction mixture was cooled below -65° C. and then 4.7 mL of 2.5 M n-BuLi/hexanes solution was added dropwise. After 15 minutes, 26 mL of 0.5 M ZnCl2 /THF solution was added dropwise. In a separate reaction flask, 67 mg of Pd(OAc)2 was added to a solution of 201 mg of tri(o-tolyl)phosphine in 5 mL of THF, and this mixture was stirred for 5 minutes before its addition, via cannula, to the main reaction mixture. A solution of 3.85 g of 2-(2,6-difluorophenyl)-4,5-dihydro-4-(4-iodophenyl)oxazole (prepared as described in WO 95/04726) in 10 mL of THF was added, and the reaction mixture was allowed to warm to room temperature and stir for 2 to 3 hours. The reaction mixture was poured into ice-cold aqueous NH4Cl and extracted with ethyl acetate. The organic phase was washed with saturated aqueous NaCl, dried over MgSO4, and concentrated under vacuum. The oily residue was adsorbed onto silica gel, applied to a column of silica gel and eluted with hexane/ethyl acetate (6:1 v:v) to obtain 3.6 g of the title compound of Step B as a viscous oil. 1H NMR (CDCl3, 300 MHz) δ 1.1 (m, 18H), 1.3 (m, 3H), 4.3 (m, 1H), 4.8 (m, 1H), 5.5 (m, 1H), 7.0 (m, 2H), 7.3-7.5 (m, 5H), 7.5-7.6 (m, 4H).

Provenance & Evidence