Trifluoroacetic acid → 5-(2-Dimethylamino-ethyl)-3-methyl-4-oxo-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carbaldehyde

Participants

Reaction Conditions

Reaction Steps

5-(2-Dimethylamino-ethyl)-3-methyl-4-oxo-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carboxylic acid tert-butyl ester 23b (774 mg, 2.3 mmol) was dissolved in trifluoroacetic acid (3.1 ml, 20 mmol) under stirring, the resulting solution was heated at 40° C. for 5 minutes in an oil bath under an argon atmosphere. The reaction mixture was cooled down to −5° C. in an ice-salt bath under stirring, added with triethoxy methane (0.5 ml, 3.0 mmol) and stirred for 2 minutes. Then the ice-salt bath was removed, and the reaction mixture was allowed to warm up to room temperature and stirred for another 1 hour. After thin lay chromatography showed the disappearance of starting materials, the reaction mixture was added with ice water (3 ml) and dichloromethane (10 ml), adjusted to pH 11 with aqueous sodium hydroxide solution (2 mol/L) and extracted with dichloromethane (10 ml×3). The combined organic extracts were dried over anhydrous magnesium sulfate, filtered to remove the drying agent and concentrated under reduced pressure to obtain a henna oil. The residue was purified by silica gel column chromatography to obtain the title compound 5-(2-dimethylamino-ethyl)-3-methyl-4-oxo-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carbaldehyde 23c (223 mg, yield 37%) as a yellow oil.

Provenance & Evidence