Ammonium Hydroxide → (R)-5-Hydroxy-1,3-dihydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one

Participants

Reaction Steps

A solution of sodium nitrite (275 mg, 3.98 mmol) in water (1.6 mL) was slowly added to a cooled mixture of (2R)-5-Amino-1,3-dihydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (1.00 g, 3.98 mmol, Intermediate 1) in 10% H2SO4 (0.8 mL conc H2SO4+7.2 mL water) at 0° C. The ice bath was removed and the stirred reaction was allowed to warm to ambient temperature. The reaction was then placed into a 70° C. oil bath and heated to 100° C. Bubbling was observed and heating was continued until LCMS analysis showed a completed reaction. The reaction was slowly quenched/neutralized with concentrated aqueous NH4OH (about 2 mL) such that the pH was about 8 at the end of multiple sonication/heating cycles in order to produce a stable pH and a solid suitable for filtration. The solid was collected by filtration and washed with water. The solid was then air dried and chromatographed by first mixing with about twice the amount of silica and then dry loading on a silica gel column. The product was eluted with 10% MeOH/DCM. Pooling and concentration of the product containing fractions provided the title compound. MS: m/z=253 (M+1).

Provenance & Evidence