1-Methoxyprop-1-enoxy(trimethyl)silane → methyl 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2-methyl-3-phenylpropanoate

Participants

Reaction Steps

(a)(b) To a solution of (1-(4-fluorophenyl)-1H-indazol-5-yl)(phenyl)methanol (800 mg, 2.5 mmol) and (1-methoxyprop-1-enyloxy)trimethylsilane (1 mL, 6.25 mmol) in 30 mL of dry DCM was added TiCl4 (2.5 mL of 1.0 M DCM solution, 2.5 mmol) and then stirred 1 h. The reaction was quenched with MeOH, poured into aqueous sodium bicarbonate and extracted 2× EtOAc. The organic layers were dried over MgSO4, filtered, concentrated to give methyl 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2-methyl-3-phenylpropanoat. Crude methyl 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2-methyl-3-phenylpropanoate was heated to 100 C overnight in a mixture of 2 M NaOH/MeOH/DMSO (1:1:1). The next day, the reaction was cooled, acidified to pH 5 with HCl and extracted 2× EtOAc. The organic layers were washed with water×2, dried over MgSO4, filtered, concentrated in vacuo, and purified by HPLC to give 770 mg (82% yield, 2 steps) of acid 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2-methyl-3-phenylpropanoic acid which could be separated into its four isomers by chiral HPLC. MS found: (M+H)+=375.

Provenance & Evidence