3-Fluorobenzylamine → 2-(Dimethylaminomethyl)-N-[(3-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic acid amide

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 530 mg (1.56 mmol) 2-((dimethylamino)methyl)-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acid ethyl ester in toluene (33 ml) were added 5.5 ml (2M solution in toluene, 10.9 mmol) Me3Al at RT followed by the addition of 1.77 g (15.6 mmol) 3-fluorobenzylamine. The reaction mixture was heated at 120° C. for 2 d. Then the reaction was quenched with water and acidified to pH ˜2 with conc. aq. HCl. After washing with EtoAc the aqueous layer was basified with NaOH to pH ˜11. The solution was then extracted twice with EtOAc. The combined organic layers were washed with water and brine, dried over MgSO4 and concentrated in vacuum. After CC (EtOAc/hexane 1:1->EtOAc/MeOH 9:1) of the residue, 60 mg (0.14 mmol, 9%) 2-(Dimethylaminomethyl)-N-[(3-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic acid amide (example 31) were obtained. MS: m/z 420.2 [M+H]+.

Provenance & Evidence