Sodium Carbonate → 1H-indole-6-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a mixture of methyl 2-bromo-7-chloro-3-cyclohexyl-1H-indole-6-carboxylate (841.8 mg, 2.27 mmol), phenylboronic acid (409 mg, 3.35 mmol), Pd(PPh3)4 (267 mg, 0.231 mmol), LiCl (188 mg, 4.44 mmol) and Na2CO3 (589 mg, 5.56 mmol) under N2 at r.t. in a re-usuable sealed tube was charged with a mixture of PhMe/EtOH (10 ml/10 ml) and then water (6.6 ml). The sealed tube was closed and the reaction mixture stirred at 60° C. for 3 hr, left standing at r.t. overnight, and then re-stirred at 60° C. for 2 hr 40 min. After cooling to r.t., the mixture was partitioned between CH2Cl2 and H2O (50 ml/50 ml). The organic layer was separated and evaporated to give a residue, which was purified by Biotage flash chromatography (gradient elution, 0 to 20% EtOAc/Hexane) to gave 1H-indole-6-carboxylic acid, 7-chloro-3-cyclohexyl-2-phenyl-, methyl ester (755 mg, 90%). 1H NMR (500 MHz): (CD3OD) δ 7.77 (d, J=8.3, 1H), 7.61 (d, J=8.3, 1H), 7.58-7.52 (overlapping m, 4H), 7.47 (m, 1H), 3.95 (s, 3H), 2.92 (m, 1H), 2.03 (m, 2H), 1.88-1.78 (overlapping m, 5H), 1.38 (m, 3H); Analytical HPLC method: Solvent A=10% MeOH-90% H2O-0.1% TFA, Solvent B=90% MeOH-10% H2O-0.1% TFA, Start % B=0, Final % B=100, Gradient time=2 min, Flow Rate=5 ml/min, Column: Xterra MS C18 S7 3.0×50 mm; LC/MS: (ES+) m/z (M+H)+=368.06, 370.03, HPLC Rt=2.085 min.

Provenance & Evidence