Dibenzylamine → Tert-butyl 4-[(dibenzylamino)carbonyl]piperidine-1-carboxylate

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([OH:16])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:17]([NH:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(N(C(C)C)CC)(C)C.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>>[CH2:25]([N:24]([CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:14]([CH:11]1[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:13][CH2:12]1)=[O:16])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

Reactant 4

HCID 7656Dibenzylamine

HCID 81531Diisopropylethylamine

HCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acid

HCID 2733179PyBroP

Product 1

HCID 22236495Tert-butyl 4-[(dibenzylamino)carbonyl]piperidine-1-carboxylateYield 75%

Procedure

To a stirred mixture of 1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid (J. Med. Chem. 1998, 41, 2492–2502, 3.0 g, 13.1 mmol), dibenzylamine (2.5 mL, 13.1 mmol) and diisopropylethylamine (3.4 mL, 19.7 mmol) in dichrolomethane (150 mL) was added PyBroP (bromo-tris-pyrrolidino-phosophonium hexafluorophosphate) (6.1 g, 15.7 mmol) was added at 0° C. The mixture was stirred at ambient temperature for 18 h and partitioned between dichloromethane and water. After extraction with dichloromethane, the combined organic phase was dried over magnesium sulfate and concentrated. The residue was purified by flash column chromatography on silica gel eluting with hexane/ethyl acetate (6:1) to afford 4.0 g (75%) of the title compound as a colorless amorphous powder.