(2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid → Quinoxaline

Participants

Reaction Steps

To a solution of N-Boc-trans-4-hydroxy-L-proline 2-11 (2.404 g, 10.396 mmol) in DMF (14 ml) and THF (60 ml) at 0° C. was added t-BuONa (3.0 g, 31.189 mmol) portionwise. The reaction mixture was allowed to warm up to rt. After stirring for 1 h, the mixture was cooled down to 0° C. and 2-chloro-3-(1,1-difluoroallyl)quinoxaline 2-10 (2.45 g, ˜10.396 mmol) was added and warmed up to rt. After stirring for 4 h, the reaction mixture was quenched with 1 N HCl at 0° C. The aqueous layer was extracted with EtOAc (3×), and the organic layer was combined, washed with water, brine, dried and concentrated in vacuo. To the residue in DCM (50 ml) and MeOH (10 ml) was added TMSCHN2 (10.4 ml, 20.792 mmol, 2.0 M in Hexane). The solution was stirred at rt for 30 min then concentrated in vacuo. The residue was purified by flash chromatography on CombiFlash with Hexane to 30% ethyl acetate in hexane to afford desired product 1-1 (3.84 g, 82%). MS (ESI): m/z=450.24 [M+H].

Provenance & Evidence