Water → Tert-butyl 4-methoxypiperidine-1-carboxylate
Reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:17]I.O>CN(C=O)C.[Cl-].[Na+].O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][CH3:17])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]Participants
Procedure
To a vigorously stirred solution of 4-hydroxypiperidine-1-carboxylic acid tert-butyl ester (2.07 g, 10.3 mmol) in DMF (25 mL) was added a 60% sodium hydride dispersion in mineral oil (500 mg, 12.5 mmol). After stirring for 20 min, methyl iodide (0.9 mL, 14.5 mmol) was added and the resulting mixture stirred for 48 h before being added to a mixture of water and brine (250 mL, 1:1). Extraction with ethyl acetate (4×50 mL), washing of the combined extracts with brine (100 mL) and drying (MgSO4) gave, after concentration, a residue which was purified via flash chromatography (silica gel, ethyl acetate/hexane, 1:1) to give the title compound as a colourless oil. δH (CDCl3): 1.50 (9H, s), 1.52, 1.88 (4H, 2m) 3.12 (2H, ddd), 3.18 (1H, m), 3.19 (3H, s), 3.77 (2H, m); Rf 0.33 (ethyl acetate/hexane: 1/1).
Workup
- stirringthe resulting mixture stirred for 48 h
- extractionExtraction with ethyl acetate (4×50 mL)
- washwashing of the combined extracts with brine (100 mL)
- dry with materialdrying (MgSO4)
- customgave
- concentrationafter concentration
- customa residue which was purified via flash chromatography (silica gel, ethyl acetate/hexane, 1:1)
Sources & evidence
- ORD record
- ord-6416550690bd410986eb0fde07ece2d3
- Source dataset
- uspto-grants-2012_04
- Patent number
- US08158622B2
Reaction notes
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