(2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid → HCID 58005112, compound

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Reaction Steps

To a solution of trans 4-hydroxy L-BOC-proline (1 eq) in DMSO (0.2 M) at RT was added tBuOK (3 eq) in a single portion. The reaction mixture was stirred at RT for 30 min, cooled to 10° C. and 7-bromo-1-chloroisoquinoline was added (1 eq). The resulting mixture was allowed to warm to RT and stirred overnight. The organic layer was washed with citric acid 10% solution, water and brine and the aqueous phases were back extracted with EtOAc. The combined organic phases were dried (Na2SO4) and the solvent evaporated under reduced pressure to give a dark solid that was dissolved in MeOH. To the stirred solution, trimethylsilyldiazomethane 2.0 M in hexanes (4.0 eq.) was added dropwise at 15° C. The resulting mixture was stirred for 15 min after gas evolution has ceased. Volatiles were removed by rotary evaporation and the residue was purified by flash chromatography (HORIZON system, column SiO2, eluent: PE:EtOAc with EtOAc (from 60 to 80%) to give the title product 85 as a solid (71%). MS (ES+) m/z 452 (M+H+).

Provenance & Evidence