Water → Tert-butyl 2-benzyl-4-cyanopiperidine-1-carboxylate
Reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH:9]1[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(C)C=CC(S([CH2:31][N+:32]#[C-])(=O)=O)=CC=1.CC(C)([O-])C.[K+].O>COCCOC>[CH2:15]([CH:9]1[CH2:10][CH:11]([C:31]#[N:32])[CH2:12][CH2:13][N:8]1[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1Participants
Conditions
- Temperature
- -10 °C
Procedure
To a solution of 2-benzyl-4-oxo-piperidine-1-carboxylic acid tert-butyl ester (15 g, 51.8 mmol) (from SYNTECH) in DME (250 mL) under nitrogen atmosphere was simultaneously added toluene-4-sulfonylmethyl isocyanide (15.2 g, 77.7 mmol, in 250 mL DME) and potassium tert-butoxide (156 mL, 1 M in tert-butanol) over 1 h so that the temperature was kept below −10° C. The solution was stirred at −10° C. for 2 h and then allowed to reach room temperature over 16 h. To the reaction mixture was added H2O (400 mL) and the solution was stirred for 20 min and then extracted with DEE (×3) and EtOAc (×3). The combined organic phases were dried over Na2SO4 and evaporated. The residue was purified by column chromatography using EtOAc/heptane (10-60% gradient EtOAc) to yield tert-butyl 2-benzyl-4-cyanopiperidine-1-carboxylate (11.85 g, 76%). 1H NMR (600 MHz, cdcl3) δ 1.38-1.46 (m, 9H), 1.63-2.14 (m, 4H), 2.62-3.33 (m, 4H), 4.17 (m, 1H), 4.48 (m, 1H), 7.11-7.41 (m, 5H); MS m/z 301 (M+H)+.
Workup
- customover 1 h
- customwas kept below −10° C
- waitto reach room temperature over 16 h
- stirringthe solution was stirred for 20 min
- extractionextracted with DEE (×3) and EtOAc (×3)
- dry with materialThe combined organic phases were dried over Na2SO4
- customevaporated
- customThe residue was purified by column chromatography
Sources & evidence
- ORD record
- ord-586ff0ead96d4fc7b09c7592e7c69f86
- Source dataset
- uspto-grants-2013_04
- Patent number
- US08415378B2
Reaction notes
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