Hydrogen Bromide → (2R)-5-bromo-1,3-dihydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one

Participants

Reaction Conditions

Reaction Steps

To a cooled 0° C. solution of (R)-5-Amino-1,3-dihydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (0.5 g, 2 mmol, Intermediate 1), in 48% HBr (4 mL) was added slowly over 10 minutes a solution of sodium nitrite (137 mg, 2 mmol) in water (0.6 mL with a 0.2 mL wash). After 5 minutes CuBr (285 mg, 2 mmole) was added and a condenser with nitrogen flow was attached. The reaction mixture was placed into a 100° C. bath and heated to 100° C. for 20 minutes. The reaction was diluted with water to obtain a large amount of precipitate. The reaction was quenched with concentrated aqueous NH4OH (about 2.5 mL) and the subsequently formed solid was collected by filtration and washed with water. The solid was air dried to obtain 740 mg of a free flowing solid, to which was added about 2 g of silica gel. The mixture was dry-loaded onto a silica gel column and the product was eluted using a tertiary solvent mixture/gradient (10-70%/80%-20%/10% EtOAc/Hex/DCM). The product containing fractions were combined and concentrated at reduced pressure to give the title compound. MS: m/z=315 (M+1).

Provenance & Evidence