(S)-1-Boc-3-methylpiperazine → HCID 66582778, compound

Participants

Reaction Conditions

Reaction Steps

A 100 mL round-bottomed flask was charged with tert-butyl (3S)-3-methyl-1-piperazinecarboxylate (10.0 g, 49.9 mmol), 2-(4-bromophenyl)-1,1,1-trifluoro-2-propanol (13.43 g, 49.9 mmol, Example 27, step 1), sodium tert-butoxide (10.56 g, 110 mmol) and 100 mL of toluene. To this was added dicyclohexyl(2′,6′-diisopropoxybiphenyl-2-yl)phosphine (RuPhos) (1.864 g, 3.99 mmol, Strem Chemical Inc, Newburyport, Mass.), tris(dibenzylideneacetone)dipalladium (0) (1.83 g, 2.00 mmol, Strem Chemical Inc, Newburyport, Mass.). The mixture was heated at 100° C. for 12 h then diluted with water (100 mL) and extracted with EtOAc (2×200 mL). The combined extracts were dried (MgSO4) and purified by column chromatography (330 g of silica, 0 to 50% EtOAc in hexanes) to give tert-butyl (3S)-3-methyl-4-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-1-piperazinecarboxylate (13.05 g) as a white solid.

Provenance & Evidence