Dimethyl Sulfate → N-Boc-2-Methyl-Piperidine
Reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[CH3:14]N(CCN(C)C)C.[Li]C(CC)C.S(OC)(OC)(=O)=O>CCOCC.O>[C:1]([N:8]1[CH2:9][CH2:10][CH2:11][CH2:12][CH:13]1[CH3:14])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]Participants
Conditions
- Temperature
- -78 °C
Procedure
A solution of N-Boc-Piperidine (15.0 g, 80.95 mmol) in ether (160 mL) was cooled to −78° C. and treated with TMEDA (15.9 mL, 105.2 mmol) followed by sec-BuLi (85 mL, 105.2 mmol) dropwise. The mixture was stirred for 3 h at −78° C. and then treated with a solution of dimethyl sulfate (15.3 mL, 161.9 mmol) in 65 mL of ether. The mixture was warmed to room temperature and then was diluted with water and extracted with ether. The combined extracts were dried over K2CO3 and then concentrated to give a crude product as a colorless oil. The product was purified by column chromatography on silca gel with 5% EtOAc/hexane to afford 16.0 g (81%) of product as a clear oil which was homogeneous by TLC analysis. 1H NMR (300 MHz) δ 4.33 (m, 1H), 3.92-3.81 (pair of br. d, 1H), 2.81-2.72 (dt, 1H), 1.60-1.36 (m, 15H), 1.09-1.07 (d, 3H); 13C NMR (75 MHz) 154.9 (s), 78.6 (s), 45.9 (s), 38.6 (s), 29.9 (s), 28.4 (s), 25.6 (s), 18.6 (s), 15.6 (s) ppm.
Workup
- temperatureThe mixture was warmed to room temperature
- extractionextracted with ether
- dry with materialThe combined extracts were dried over K2CO3
- concentrationconcentrated
- customto give a crude product as a colorless oil
- customThe product was purified by column chromatography on silca gel with 5% EtOAc/hexane
Sources & evidence
- ORD record
- ord-9a39cc02c7094effb012a6d7b684552b
- Source dataset
- uspto-grants-2012_05
- Patent number
- US08168657B2
Reaction notes
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