Methyl chloroformate → 1-Tert-butyl 4,4-dimethyl piperidine-1,4,4-tricarboxylate
Reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[N:13]1([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:18][CH2:17][CH:16]([C:19]([O:21][CH3:22])=[O:20])[CH2:15][CH2:14]1.Cl[C:31]([O:33][CH3:34])=[O:32]>C1COCC1>[N:13]1([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:14][CH2:15][C:16]([C:31]([O:33][CH3:34])=[O:32])([C:19]([O:21][CH3:22])=[O:20])[CH2:17][CH2:18]1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
To a chilled solution of diisopropylamine (3.5 mL, 24.7 mmol) in THF (20 mL) at −78° C. was added n-BuLi (2M in hexane, 14.8 mL, 1.2 equiv.). The reaction mixture was stirred for 1 h. A solution of 1-tert-butyl 4-methyl piperidine-1,4-dicarboxylate (5 g, 20.6 mmol, 1 equiv.) in THF (15 mL) was added dropwise at −78° C. The reaction mixture was stirred for 1 h. Methyl chloroformate (1.7 mL, 22.6 mmol, 1.1 equiv.) was added to the above mixture. The reaction mixture was warmed to rt slowly while stirring. After 3 h, the reaction mixture was quenched with saturated NH4Cl and extracted with ethyl acetate. The organic layer was dried over Na2SO4 and concentrated to give 1-tert-butyl 4,4-dimethyl piperidine-1,4,4-tricarboxylate (6.2 g, quant.), which was used without further purification. LRMS (M+H+-Boc) m/z 202.1.
Workup
- stirringThe reaction mixture was stirred for 1 h
- stirringwhile stirring
- waitAfter 3 h
- customthe reaction mixture was quenched with saturated NH4Cl
- extractionextracted with ethyl acetate
- dry with materialThe organic layer was dried over Na2SO4
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-2be54caaaada40ad91216af99202425e
- Source dataset
- uspto-grants-2011_12
- Patent number
- US08071625B2
Reaction notes
Loading…