Ethyl 4-piperidinecarboxylate → (R)-1-(4-(3-(1-Methyl-6-oxo-1,6-dihydropyridin-3-yl)-3-oxo-1-o-tolylpropyl)phenyl)piperidine-4-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of (R)-5-(3-(4-bromophenyl)-3-o-tolylpropanoyl)-1-methylpyridin-2(1H)-one (example 223, step 3; 500 mg, 1.22 mmol) in toluene (7 mL) was added ethyl piperidine-4-carboxylate (293 mg, 1.83 mmol), sodium tert-butoxide (234 mg, 2.44 mmol), tris(di-benzylideneacetone)dipalladium(0) (22.3 mg, 24.4 μmol) and 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (23.7 mg, 48.7 μmol) and the reaction mixture was stirred for 1 h at 85° C. The reaction mixture was evaporated and the residue chromatographed to afford the title compound (101 mg, 18%; light yellow foam, MS (ESI−): m/z=: 457.4 [M−H]−) and (R)-methyl 1-(4-(3-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-3-oxo-1-o-tolylpropyl)phenyl)piperidine-4-carboxylate (174 mg, 30%; light yellow foam, MS (ESI+): m/z=: 487.4 [M+H]+).

Provenance & Evidence