5-Bromo-2-chloroanisole → Tert-butyl 2-(4-chloro-3-methoxyphenyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of tert-butyl hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate (205 mg, 0.97 mmol), 5-Bromo-2-chloroanisole (235 mg, 1.06 mmol), Sodium tert- butoxide (130 mg, 1.35 mmol), rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (30.1 mg, 0.05 mmol) and Tris(dibenzylideneacetone)dipalladium(0) (44.2 mg, 0.05 mmol) in toluene (10 mL) under a nitrogen atmosphere was stirred at 90 °C for 12h. The solution was washed with saturated NaHCO3 solution, brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was loaded on a 24g silica gel column and purified on a Teledyne Isco instrument, eluting with 20% to 40% ethyl acetate in heptane to provide tert-butyl 5-(4-chloro-3-methoxyphenyl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate (220 mg, 64.6 %) as a solid. Used directly for the next step. MS m/z 353.3 [M+H]+ (ESI)

Provenance & Evidence