tert-Butyl acetate → methyl 2-(tert-butoxy)-2-(1,6-dimethyl-7-oxo-4-(p-tolyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetate

Participants

Reaction Steps

An ice cold solution of methyl 2-(1,6-dimethyl-7-oxo-4-(p-tolyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)-2-hydroxyacetate (28 mg, 0.082 mmol) in tert-butyl acetate (1111 μl, 8.23 mmol) was treated with perchloric acid (7.07 μl, 0.082 mmol), and stirred for 20 min. The reaction was then kept in the refrigerator without stirring for 2 days. The reaction was quenched with sat. NaHCO3 at 0° C., extracted with EtOAc 2×, washed with Brine, dried with Na2SO4, filtered, and concentrated. Purification with column chromatography (0-100% EtOAc/Hexane) gave methyl 2-(tert-butoxy)-2-(1,6-dimethyl-7-oxo-4-(p-tolyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetate (23.6 mg, 0.060 mmol, 72.4% yield). The intermediate was dissolved in Methanol (500 μl) and Tetrahydrofuran (THF) (500 μl), treated with 2M LiOH (174 μl, 0.348 mmol), and stirred at 60° C. for 4 hours. The mixture was concentrated and purified with reverse phase chromatography (20-100% MeCN/H2O-0.1% TFA, 12 min) to give title compound (19.6 mg, 0.051 mmol, 87% yield) as white solid: 1H NMR (400 MHz, CHLOROFORM-d) ppm 0.99 (s, 9H), 2.43 (s, 3H), 3.66 (s, 3H), 4.20 (s, 3H), 5.45 (s, 1H), 5.98 (d, J=2.7 Hz, 1H), 6.96 (d, J=2.7 Hz, 1H), 7.24-7.31 (m, 2H), 7.31-7.38 (m, 1H), 7.49-7.57 (m, 1H); LCMS (m/z) ES+=383 (M+1).

Provenance & Evidence