Potassium Carbonate → {1-[2-(4-Methyl-piperidin-1-yl)-ethyl]-piperidin-4-yl}-carbamic acid tert-butyl ester

HRID 1928979Notes

Reaction equation

HRID 1928979 reaction equation
[C:1]([O:5][C:6](=[O:17])[NH:7][CH:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15]O)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[CH3:18][CH:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1.CCN(C(C)C)C(C)C.[I-].C(C[P+](C)(C)C)#N.C([O-])([O-])=O.[K+].[K+]>C(#N)CC>[C:1]([O:5][C:6](=[O:17])[NH:7][CH:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][N:22]2[CH2:23][CH2:24][CH:19]([CH3:18])[CH2:20][CH2:21]2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 5

HCID 11430Potassium CarbonateHCID 693814-MethylpiperidineHCID 81531DiisopropylethylamineHCID 10514344(Cyanomethyl)trimethylphosphanium iodideHCID 45076484[1-(2-Hydroxy-ethyl)-piperidin-4-yl]-carbamic acid tert-butyl ester

Product 1

HCID 66841138{1-[2-(4-Methyl-piperidin-1-yl)-ethyl]-piperidin-4-yl}-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 7854PropionitrileSolvent

Procedure

A mixture of ester 8 (3 g, 12.28 mmol), 4-methyl piperidine (1.46 ml, 12.28 mmol) and DIEA (2.7 ml, 15.96 mmol) in 30 ml of propionitrile is treated with solid cyanomethyl-trimethyl-phosphonium iodide (3.58 g, 14.74 mmol) and heated at reflux for 3 hours. After cooling to room temperature, a 2M-K2CO3 solution is added until basic and the mixture is extracted twice with DCM. The organic layers are washed with brine, dried over anhydrous sodium sulfate and evaporated. The crude material is purified by chromatography using EtOAc/MeOH (saturated with ammonia): 9/1.

Workup

  1. temperatureheated
  2. temperatureat reflux for 3 hours
  3. extractionis extracted twice with DCM
  4. washThe organic layers are washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customevaporated
  7. customThe crude material is purified by chromatography

Sources & evidence

ORD record
ord-65ccf13c7b9c4f4799bf301f2c6279b8
Source dataset
uspto-grants-2012_05
Patent number
US08183366B2

Reaction notes

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