Hydrochloric Acid → HCID 59215785, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of (3S,8aS)-3-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)octahydropyrrolo[1,2-a]pyrazine (D82, 157 mg, 0.58 mmol) in 2.5 mL of toluene were added 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide [WO 2005/002577] (238 mg, 0.45 mmol) (t-Bu3P)2Pd (46 mg, 0.09 mmol), a 25% aqueous solution of cetyltrimethylammonium chloride (26 μL), and, at last, 50% aqueous NaOH (54 μL). The reaction deoxygenated by freeze-pump-thaw cycles and then heated to 90° C. for 7 h. The reaction was checked by UPLC/MS, showing the expected product peak at 0.84 min, with m/z=767 (M+1) and 384 ((M+2)/2). The solution was diluted with EtOAc, washed with sat. NaHCO3 and brine. The sample was purified by flash chromatography (silica, cyclohexane:EtOAc 90:10 to 0:100). Isolated 251 mg of O-TBDMS protected intermediate. The intermediate was dissolved in 11 mL of MeOH and 0.55 mL of conc. HCl were added. The reaction was left at room temperature for 1 h. The product was isolated by SCX cartridge. Isolated 140 mg of the title compound.

Provenance & Evidence