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

Participants

Reaction Conditions

Reaction Steps

3-Methyl-4-oxo-5-(2-pyrrolidin-1-yl-ethyl)-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carboxylic acid tert-butyl ester 28b (3.562 g, 9.87 mmol) was dissolved in 50 ml of dichloromethane under stirring, and added with trifluoroacetic acid (19.7 ml, 260 mmol) to the solution at room temperature. Upon the completion of the addition, the mixture was heated to reflux for 30 minutes in an oil bath. After thin lay chromatography showed the disappearance of starting materials, the reaction mixture was cooled down to −5° C. in an ice-salt bath, added with triethoxy methane (2.96 ml, 14.8 mmol) in one portion, stirred at −5° C. for 5 minutes, for another 1 hour at room temperature. The reaction system was added with water (25 ml), adjusted to about pH 11 with dilute sodium hydroxide solution (2 mol/L) and extracted with dichloromethane (100 ml×3). The combined organic extracts were concentrated under reduced pressure to obtain a henna oil. The oil was purified by silica gel column chromatography to obtain the title compound 3-methyl-4-oxo-5-(2-pyrrolidin-1-yl-ethyl)-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carbaldehyde 28c (1.116 g, yield 49%) as a yellow solid.

Provenance & Evidence