Hydrochloric Acid → HCID 68690971, compound

Participants

Reaction Conditions

Reaction Steps

To a mixture of (R)-2-N-(t-butoxycarbonyl)-10-bromo-8-trifluoromethyl-1,2,3,4,11,11a-hexahydropyrazino[1,2-b]isoquinolin-6-one (61 mg, 0.135 mmol) and 2,4,6-trivinylcyclotriboroxane pyridine complex (33 mg, 0.135 mmol) in DME (2 mL) was added K2CO3 (20 mg, 0.135 mmol) and water (1 mL). The mixture was degassed under reduced pressure and purged with argon; tetrakis(triphenylphospine)palladium (0) (20 mg, 0.135 mmol) was added. The reaction mixture was heated to 90° C. for 18 h. The reaction was cooled to room temperature, and diluted with EtOAc (50 mL). The EtOAc layer was dried over Na2SO4, filtered, and concentrated in vacuo to afford crude alkene 6a as a yellow oil. MS (ESI) 340 (M+H). Crude (R)-2-N-(t-butoxycarbonyl)-10-ethyl-8-trifluoromethyl-1,2,3,4,11,11a-hexahydropyrazino[1,2-b]isoquinolin-6-one was dissolved in EtOH (2 mL) and hydrogenated [10% Pd/C (50 mg), H2 (30 psi)]. The reaction mixture was filtered through diatomaceous earth, and then purified by flash column chromatography (silica gel, 4:1 hexanes/EtOAc). The resulting material was deprotected using 4 N HCl in 1,4-dioxane (200 μL, 0.8 mmol), followed by trituration with diethyl ether, to provide the desired product (18 mg, 40% over 3 steps) as a white solid. MS (ESI) 299 (M+H).

Provenance & Evidence