Hydrochloric Acid → 6-Oxo-2,3,6,7,8,9-hexahydro-1H-10-aza-cyclohepta[e]indene-10-carboxylic acid isopropyl ester

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Reaction Conditions

Reaction Steps

Add a solution of 4-[(3-ethoxycarbonyl-propyl)-isopropoxycarbonyl-amino]-indan-5-carboxylic acid methyl ester (510 mg, 1.30 mmol) in tetrahydrofuran (20.4 mL) to a solution of potassium tert-butoxide (2.60 mL, 2.60 mmol, 1M in tetrahydrofuran) in tetrahydrofuran (18 mL) at room temperature under an atmosphere of nitrogen. After 30 min, pour the mixture into ice/water. Treat the aqueous phase with 1M HCl to pH neutral and extract with dichloromethane. Dry the organic layer over anhydrous sodium sulfate, filter, and remove the solvent under reduced pressure. Dissolve the former crude in dimethyl sulfoxide (11 mL) and add water (2 drops) followed by addition of lithium chloride (134 mg, 3.2 mmol) and heat the resulting solution at 160° C. for 30 minutes. Cool the mixture to room temperature and pour into brine. Extract the mixture with ethyl acetate. Dry the organic layers over anhydrous sodium sulfate, filter and remove the solvent under reduced pressure. Purify the residue by flash chromatography, eluting with hexanes/ethyl acetate, to afford the title compound (302 mg, 81% over two steps). MS (ES+): 288 (M+H).

Provenance & Evidence