Diphosgene → 4-Phenyl-piperidine-1-carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)-phenyl ester
Reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=2)=[N:6][CH:7]=1.C(N(C(C)C)C(C)C)C.ClC([O:28][C:29](Cl)(Cl)Cl)=O.[C:33]1([CH:39]2[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]2)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>C(Cl)Cl>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]2[CH:10]=[CH:11][C:12]([O:15][C:29]([N:42]3[CH2:43][CH2:44][CH:39]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)[CH2:40][CH2:41]3)=[O:28])=[CH:13][CH:14]=2)=[N:6][CH:7]=1Participants
6
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -30 °C
Procedure
To a solution of 4-(5-methyl-pyridin-2-ylmethyl)phenol (0.8 mmol) prepared as described above and ethyldiisopropylamine (1.5 mmol) in CH2Cl2 (5 mL) at −30° C. was added trichloromethyl chloroformate (1.0 mmol). The solution was stirred at −30° C. for 10 min and at reflux temperature for 2 h. The solution was evaporated to dryness and redissolved in CH2Cl2 (5 mL) and cooled to 0° C. before addition of 4-phenylpiperidine (1.5 mmol). The solution was stirred at room temperature for 16 h evaporated to give the crude product which was purified by FC (Quad flash 40 CH2Cl2:Et2O:Heptane:Et3N 1:1:2:0.25->1:1:1:0.25) to give the title compound in 28% yield as an oil.
Workup
- customat −30° C.
- temperatureat reflux temperature for 2 h
- customThe solution was evaporated to dryness
- dissolutionredissolved in CH2Cl2 (5 mL)
- stirringThe solution was stirred at room temperature for 16 h
- customevaporated
- customto give the crude product which
- customwas purified by FC (Quad flash 40 CH2Cl2:Et2O:Heptane:Et3N 1:1:2:0.25->1:1:1:0.25)
Sources & evidence
- ORD record
- ord-cfb4e9480a7c4414861481fc4c3c9059
- Source dataset
- uspto-grants-2007_10
- Patent number
- US07279470B2
Reaction notes
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