Benzyl 3-(2-amino-1-(6-(3-(tert-butyldimethylsilyloxy)pyrrolidin-1-yl)-1H-indol-3-yl)ethyl)-2-methylphenylcarbamate → ethyl 4-(3-(benzyloxycarbonylamino)-2-methylphenyl)-7-(3-(tert-butyldimethylsilyloxy)pyrrolidin-1-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-1-carboxylate

Participants

Reaction Steps

To a solution of benzyl 3-(2-amino-1-(6-(3-(tert-butyldimethylsilyloxy)pyrrolidin-1-yl)-1H-indol-3-yl)ethyl)-2-methylphenylcarbamate (0.1010 g, 0.169 mmol) in 1,4-dioxane (4.82 mL) was added 50% ethyl 2-oxoacetate/toluene (0.067 mL, 0.337 mmol) at 10° C. The cold bath was removed, and the reaction was stirred to room temperature for 3 h. The reaction was concentrated in vacuo to give crude ethyl 4-(3-(benzyloxycarbonylamino)-2-methylphenyl)-7-(3-(tert-butyldimethylsilyloxy)pyrrolidin-1-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-1-carboxylate which was used in the subsequent step. This was added to p-xylene (41.6 mL) and 10% Pd/C (0.310 g, 0.291 mmol). The reaction was heated to 125° C. for 4.5 hr and cooled to room temperature. The solution was filtered through a pad of CELITE® and rinsed with EtOAc (150 mL). The filtrate was washed with water (40 mL), dried over MgSO4, filtered and concentrated in vacuo to give a residue which was purified by flash chromatography using an ISCO 120 g column eluting with 0-30% EtOAc/CH2Cl2. Appropriate fractions (20% elution) were combined, concentrated in vacuo to give the desired product (0.1487 g, 0.219 mmol, 15.0% yield) as a tan solid.

Provenance & Evidence