Picolinic acid → HCID 16118896, compound

Participants

Reaction Steps

A mixture of (4S,7R)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 19; 1.24 g, 6 mmol), 1-chloro-2-iodobenzene (666 μL, 5.4 mmol), copper(I) iodide (57 mg, 0.3 mmol), picolinic acid (150 mg, 1.2 mmol), and potassium bicarbonate (840 mg, 8.4 mmol) in N,N-dimethylformamide (20 mL) was irradiated in a microwave oven at 200° C. for 160 min. The reaction mixture was diluted with 0.1 M HCl (200 mL) and then extracted with ethyl acetate (200 mL). The organic layer was washed with 0.1 M HCl, 0.25 M NaOH, and brine, then dried (magnesium sulfate), filtered, evaporated and purified using an ISCO CombiFlash® Sg100c chromatography system, eluting with 5-100% ethyl acetate/dichloromethane to give a tan semi-solid which was taken up in ethyl acetate and washed with 0.1 M HCR. The solvent was evaporated and the residue was recrystallized from ethyl acetate. The mother liquor was evaporated and the residue recrystallized from ethyl acetate. The crystals were combined to give (4S,7R)-2-(2-chloro-phenyl)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (80 mg, 5%) as a white solid. APCI-MS (M+H) 317.

Provenance & Evidence