Potassium Carbonate → (R)-5-(benzyloxy)-2-(4-(benzyloxy)phenyl)-1-(4-(2-(3-(fluoromethyl)pyrrolidin-1-yl)ethoxy)benzyl)-3-methyl-1H-indole

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-(4-((5-(benzyloxy)-2-(4-(benzyloxy)phenyl)-3-methyl-1H-indol-1-yl)methyl)phenoxy)ethyl methanesulfonate, (R)-3-(fluoromethyl)pyrrolidine (Intermediate 8) and potassium carbonate in acetonitrile was degassed with three vacuum/N2 cycles. The reaction was heated at 80° C. for 10 hrs, allowed to cool to room temperature and then diluted with water (40 mL). The aqueous layer was extracted with ethyl acetate (2×40 mL) and the combined ethyl acetate extracts were then washed with water (40 mL), washed with brine (40 mL), dried (MgSO4), filtered, concentrated and purified by silica gel chromatography (0%-5% MeOH in DCM) to give 274 mg of (R)-5-(benzyloxy)-2-(4-(benzyloxy)phenyl)-1-(4-(2-(3-(fluoromethyl)pyrrolidin-1-yl)ethoxy)benzyl)-3-methyl-1H-indole. 1H NMR (400 MHz, DMSO-d6): δ 7.48 (d, 4H), 7.44-7.37 (m, 4H), 7.37-7.32 (m, 2H), 7.30 (d, 2H), 7.21 (d, 1H), 7.15-7.10 (m, 3H), 6.81 (dd, 1H), 6.74 (s, 4H), 5.17-5.10 (m, 6H), 4.33-4.30 (m, 1H), 4.22-4.18 (m, 1H), 3.94 (t, 2H), 2.70 (t, 2H), 2.56-2.40 (m, 3H), 2.60 (t, 1H), 2.36-2.31 (m, 1H), 2.16 (s, 3H), 1.86-1.76 (m, 1H), 1.40-1.30 (m, 1H). LCMS: 655.3 (M+H)+.

Provenance & Evidence