Lithium Hydroxide → 2-Tert-butoxy-2-[4-(3,4-dimethylphenyl)-7-[(4-methoxyphenyl)methyl]-2-methyl-1-oxo-3-isoquinolyl]acetic acid

Participants

Reaction Conditions

Reaction Steps

A mixture of methyl [7-bromo-4-(3,4-dimethylphenyl)-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinyl][(1,1-dimethylethyl)oxy]acetate (34.0 mg, 0.070 mmol) and (4-methoxybenzyl)zinc(II) bromide (0.280 mL, 0.140 mmol) in N,N-Dimethylformamide (DMF) (1.2 mL) was degassed with nitrogen for 5 minutes. Pd(PPh3)4 (8.08 mg, 6.99 μmol) was added and the mixture was irradiated in the microwave at 120° C. for 20 minutes. The mixture was diluted with ethyl acetate, washed with water, followed by brine, dried over sodium sulfate, filtered and then concentrated to give a dark residue. The crude residue was treated with 2M lithium hydroxide (0.140 mL, 0.280 mmol) in Tetrahydrofuran (THF) (0.8 mL) and Methanol (0.8 mL) and then stirred at 70° C. for 30 minutes. Additional 2 M lithium hydroxide (0.200 mL, 0.400 mmol) was added and the mixture was stirred at 70° C. for 2 additional hours. The mixture was concentrated and the residue was purified by reverse phase chromatography to afford the title compound as a white solid (11 mg, 31%). 1H NMR (400 MHz, CHLOROFORM-d) δ=8.39-8.30 (m, 1 H), 7.41-7.29 (m, 2 H), 7.29-7.18 (m, 1 H), 7.17-7.09 (m, 2 H), 7.09-6.96 (m, 2 H), 6.81 (dd, J=2.0, 8.6 Hz, 2 H), 5.34 (s, 1 H), 4.04 (s, 2 H), 3.77 (s, 3 H), 3.68 (s, 3 H), 2.35 (m, 3 H), 2.30 (m, 3 H), 1.06 (m, 9 H); LC/MS (m/z) ES+=514 (M+1).

Provenance & Evidence