Triphenylphosphine → (2S,4S)-1-tert-Butyl 2-methyl 4-(((S)-2-(tert-butoxycarbonyl)-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-1,2,3,4-tetrahydroisoquinolin-7-yl)oxy)pyrrolidine-1,2-dicarboxylate

Participants

Reaction Steps

To a solution of (S)-tert-butyl 7-hydroxy-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (Compound D of Example 1, 50 mg, 0.12 mmol) in CH2Cl2 (1.0 mL) was added PPh3 (37 mg, 0.14 mmol), (2S,4R)-1-tert-butyl 2-methyl 4-hydroxypyrrolidine-1,2-dicarboxylate (Aldrich, 35 mg, 0.14 mmol) and ADDP (37 mg, 0.14 mmol). The resulting reaction mixture was allowed to stir overnight at room temperature. Additional (2S,4R)-1-tert-butyl 2-methyl 4-hydroxypyrrolidine-1,2-dicarboxylate (35 mg, 0.14 mmol), PPh3 (37 mg, 0.14 mmol) and ADDP (37 mg, 0.14 mmol) were then added. The reaction mixture was allowed to stir at room temperature for 60 h, then concentrated in vacuo and purified using flash column chromatography (gradient from 0% to 60% EtOAc/hexanes) to give the title compound (66 mg, 86%) as a colorless oil. MS (ESI+) m/z 650.4 (M+H)+.

Provenance & Evidence