Acetic Acid → tert-butyl 2-(7-hydroxy-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate

Participants

Reaction Conditions

Reaction Steps

tert-Butyl-2-(7-(benzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-ylidene)acetate (1.391 g, 3.70 mmol) was dissolved in THF (25 mL) and 10% palladium on carbon (50% in water, 217 mg) was added. The reaction mixture was placed under 225 psi of hydrogen in a hydrogenation reactor for 24 h. The mixture was filtered and the filtrate was concentrated under reduced pressure to provide tert-butyl 2-(7-(benzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate. The above material was taken up in a mixture of THF (20 mL) and EtOH (20 mL) and Pd(OH)2/C (250 mg) was added. The reaction mixture was placed under 200 psi of hydrogen in a hydrogenation reactor for 2 days. Additional Pd(OH)2/C (250 mg) was added and the reaction mixture was placed under 300 psi of hydrogen in a hydrogenation reactor for 24 h. Pd(OH)2/C (250 mg) was again added and the vessel placed under 500 psi of hydrogen in a hydrogenation reactor for 24 h. The hydrogenation reactor was warmed to 50° C. for 8 h. The reaction mixture was cooled to room temperature and AcOH (5 mL) was added. The reaction mixture was placed under 500 psi of hydrogen for 16 h. The reaction mixture was filtered through Celite® and the filtrate was concentrated under reduced pressure to provide a mixture of the title compound and tert-butyl 2-(7-hydroxy-2,3,9,9a-tetrahydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate. The title compound (150 mg) was isolated by silica gel column chromatography. tert-Butyl 2-(7-hydroxy-2,3,9,9a-tetrahydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate (600 mg) was dissolved in toluene (100 mL) and Pd/C (1.0 g) was added. The reaction mixture was warmed to 80° C. and stirred for 2 days. The reaction mixture was filtered through Celite® and the title compound (250 mg) was isolated as a white solid resulting from precipitation during concentration of the filtrate. LCMS m/z=288.3 [M+H]+.

Provenance & Evidence