Potassium Carbonate → HCID 68518393, compound

Participants

Reaction Conditions

Reaction Steps

K2CO3 (100 g) was dissolved in water (225 mL) and the resulting solution was cooled to 25-30° C. 1-[(3-bromo-4-nitrophenyl)methyl]-4-methylpiperazine dihydrochloride (50.0 g), methyl 5-amino-3-({(1R)-1-[2-(trifluoromethyl)phenyl]ethyl}oxy)-2-thiophenecarboxylate hydrochloride (53.7 g) and 2-methyl THF (250 mL) were added and the mixture was stirred until complete dissolution had taken place. The layers were separated, retaining the organic phase. 2-Methyl tetrahydrofuran (40 mL) was added and the mixture was distilled under reduced pressure to a volume of 350-400 mL. Xantphos (2.32 g, 3 mol %) was added, followed by cesium carbonate (48.0 g) and tris(benzylideneacetone)dipalladium(0) (1.84 g, 1.5 mol %). The reaction mixture was heated to 70-75° C. until judged complete by HPLC and then cooled to 20° C. Water (250 mL) was added and the mixture stirred to dissolve the inorganics. The mixture was filtered through celite, then the phases allowed to separate. The aqueous phase was discarded. The celite was washed with MeOH (200 mL). The MeOH wash was added to the previous organic phase. The mixture was slowly added to 5 M aqueous HCl over approximately 40 minutes. The resulting crystalline slurry was stirred overnight at room temperature, then filtered, washing with MeOH (100 mL, cooled to 0° C.) and dried under reduced pressure to give the title compound (72.8 g, 87% th) as orange to red crystalline sold.

Provenance & Evidence