tert-Butyl piperazine-1-carboxylate → tert-Butyl 4-(2-(ethoxycarbonyl)benzofuran-4-yl)piperazine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

tert-butyl piperazine-1-carboxylate (5.22 g, 28.04 mmol), ethyl 4-chlorobenzofuran-2-carboxylate (6.3 g, 28.04 mmol), 2-Dicyclohexylphosphino-2',4',6'-tri-iso-propyl-1,1'-biphenyl (1.337 g, 2.80 mmol), Tris(dibenzylideneacetone)dipalladium(0) (1.284 g, 1.40 mmol) and CESIUM CARBONATE (11.88 g, 36.46 mmol) were heated under argon to 95 °C 14:51:42 overnight, LC showed no s.m. EN03969-25-001. The mixture was allowed to cool to rt, diluted with EtOAc (35 mL) and filtered through a pad of Celite, washed with EtOAc (total of 100 mL). The filterate was collected and the solvent was removed by rotary evaporation. The crude product was treated with diisopropylether under stirring at rt for 4 days, the mixture was filterered and washed with diisopropylether. The diisopropyletherphase was concentrated to give 3.6 g. The solid was treated with MeOH under stirring at rt for 4 h, filtrated, washed with MeOH, still not clear solution. The solid was vacuumdried at 40 °C over night to give 7.6 g. The MeOH-mixture was filterered through a process K200 filter, the formed solution was concentrated to give 1.4 g. No pure product in any of the solids, were combined (12.6 g) and dissolved in CH2Cl2 and put on silica (200 g) using 1. CH2Cl2 (500 mL), 2. EtOAc (400 mL) as eluent. Fr. 5-6 were combined and concentrated to give EN03969-25-002 (10.6 g, 28.3 mmol, 101 %). To the brownish solid was added ether (40 mL) and the slurry was stirred at 35 °C for 5-10 min. The now grey solid was filtered off, rinsed with 4x20 mL ether and dried under vacuum at 30 °C o.n, yielding EN03969-25-003 (6.7 g, 17.89 mmol, 63.8 %). 44 mg of EN03969-25-003 was sent to **** at Analytical Services and OA Support team **** for purity-assay (95 %), see report. EN03969-25-003 was delivered to CM in can: **32649089.**

Provenance & Evidence