Toluene → HCID 86609667, compound

Participants

Reaction Steps

Combine 1-methyl-4-(3-Chloro-2-fluorophenylamino)piperidine (Preparation 19) (0.439 g, 1.8 mmol), benzophenone imine (0.393 g), Pd2(dba)3 (4.1 mg), 2-(dicyclohexylphosphino)biphenyl (4.7 mg), and sodium t-butoxide (0.242 g) with toluene (5 mL) and heat at reflux overnight. Dissolve the reaction mixture in methanol and filter through a SCX column (10 g), wash with methanol, elute the product with 2M NH3 in methanol, evaporate the solvent, and further purify on a silica gel column (35 g, using a dichloromethane-2M NH3 in methanol gradient) to give crude 1-methyl-4-(3-benzhydrylideneamino-2-fluorophenylamino)piperidine (0.372 g). Add 1N HCl (2 mL) into a solution of the benzhydrylidenyl intermediate in THF (10 mL) and stir at room temperature for 30 minutes. Basicify with NH4OH, extract with ethyl acetate, dry over anhydrous sodium sulfate, evaporate and purify on a silica gel columnn (10 g), using a gradient of dichloromethane-2M NH3 in methanol to give the title intermediate (0.08 g): mass spectrum (ion spray): m/z=224 (M+1); 1H NMR (CDCl3): 6.75 (ddd, 1H), 6.12 (m, 2H), 3.70 (br d, 1H), 3.62 (br s, 2H), 3.25 (m, 1H), 2.80 (m, 2H), 2.29 (s, 3H), 2.10 (m, 4H), 1.53 (m, 2H).

Provenance & Evidence