tert-Butyl acrylate → (E)-Benzyl 4-(4-(3-tert-butoxy-3-oxoprop-1-enyl)-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate

Participants

Reaction Conditions

Reaction Steps

To a solution of benzyl 4-(4-bromo-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate (Intermediate 164A, 80 mg, 0.12 mmol) in DMF (580 μL) and Et3N (580 μL) was added (PPh3)2PdCl2 (8 mg, 0.012 mmol) followed by tert-butyl acrylate (58 μL, 0.40 mmol). The reaction mixture was purged with N2 for 5 min and then heated at 140° C. overnight. The reaction mixture was poured into a separatory funnel containing 1N aq. HCl solution and EtOAc. The organic layer was washed 1N aq. HCl solution (2×) and the aqueous layer was extracted with EtOAc (3×). The combined organic extracts were washed with sat. aq. NaHCO3 solution, dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash chromatography (gradient from 0% to 35% EtOAc/hexanes) to provide the title compound (42 mg, 50%) as a colorless oil. MS(ESI+) m/z 733.5 (M+H)+.

Provenance & Evidence