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]=1Participants
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.
Workup
- additionwas added at 0° C
- custompartitioned between dichloromethane and water
- extractionAfter extraction with dichloromethane
- dry with materialthe combined organic phase was dried over magnesium sulfate
- concentrationconcentrated
- customThe residue was purified by flash column chromatography on silica gel eluting with hexane/ethyl acetate (6:1)
Sources & evidence
- ORD record
- ord-b42a721d2e0040f8b7854bb7dcf4dd79
- Source dataset
- uspto-grants-2006_03
- Patent number
- US07012080B2
Reaction notes
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