Ammonium Acetate → 3,4,5,6-Tetrahydro-3,10-diazabenzo[e]azulene-1-carboxylic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-oxo-1,4,5,6,7,8-hexahydro-cyclohepta(b)pyrrole-3-carboxylic acid ethyl ester (7.0 g, 31.67 mmol), 3-amino-prop-2-enal (3.37 g, 47.5 mmol) and ammonium acetate (365 mg, 4.75 mmol) in triethylamine (7 mL) is heated at 110° C. for 4 h. It is cooled to room temperature and the solid residue is dissolved in 100 mL dichloromethane and 100 mL sat. NaHCO3 solution. Layers are separated and the aqueous phase is extracted with 4:1 DCM/2-propanol (4×100 mL). Combined organic layers are dried (Na2SO4) and evaporated. Flash Chromatography on silica gel, eluting with EtOAc:triethylamine (20:1), provides 3,4,5,6-tetrahydro-3,10-diaza-benzo[e]azulene-1-carboxylic acid ethyl ester (1.6 g, 20%) as off-white solid. 1H NMR (400 MHz, CD3OD) δ1.247 (3H, t), 2.227 (2H, m), 2.631 (4H, m), 4.197 (2H, q), 7.170 (1H, m), 7.405 (1H, s), 7.686 (1H, d), 8.375 (1H, d). MS (ES+) 257 (M+1)

Provenance & Evidence