4-Chloropyridine → tert-Butyl methyl((1-(pyrimidin-4-yl)piperidin-4-yl)methyl)carbamate

HRID 1193344Notes

Reaction equation

HRID 1193344 reaction equation
[CH3:1][N:2]([CH2:10][CH:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1)[C:3](=[O:9])[O:4][C:5]([CH3:8])([CH3:7])[CH3:6].Cl[C:18]1[CH:23]=[CH:22][N:21]=[CH:20]C=1.CC[N:26](C(C)C)C(C)C>CC(O)C.C(OCC)(=O)C.C(=O)([O-])O.[Na+]>[CH3:1][N:2]([CH2:10][CH:11]1[CH2:16][CH2:15][N:14]([C:18]2[CH:23]=[CH:22][N:21]=[CH:20][N:26]=2)[CH2:13][CH2:12]1)[C:3](=[O:9])[O:4][C:5]([CH3:8])([CH3:6])[CH3:7]

Participants

7

Reactant 3

HCID 122884-ChloropyridineHCID 81531DiisopropylethylamineHCID 23004743tert-butyl N-methyl-N-(piperidin-4-ylmethyl)carbamate

Product 1

HCID 66805336tert-Butyl methyl((1-(pyrimidin-4-yl)piperidin-4-yl)methyl)carbamateYield 51%

Reagents, catalysts & solvents 3

HCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

tert-Butyl methyl(piperidin-4-ylmethyl)carbamate (1.4 mmol, 1.0 eq) and 4-chloropyridine (4.2 mmol, 3.0 eq) were dissolved in 2-propanol (5 ml) and DIPEA (7.0 mmol. 5.0 eq) and refluxed for 16 hours. After monitoring by TLC, the reaction solution was diluted with ethyl acetate and sat. sodium hydrogen carbonate solution and the phases were separated. The aqueous phase was washed with ethyl acetate. The combined organic phases were dried over magnesium sulfate, concentrated under reduced pressure and purified by column chromatography (silica gel, ethyl acetate:ethanol 10:1+ammonia solution). Yield: 51%

Workup

  1. customthe phases were separated
  2. washThe aqueous phase was washed with ethyl acetate
  3. dry with materialThe combined organic phases were dried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. custompurified by column chromatography (silica gel, ethyl acetate:ethanol 10:1+ammonia solution)

Sources & evidence

ORD record
ord-bb171c432a9b41bb922c24e5ec84f199
Source dataset
uspto-grants-2014_03
Patent number
US08680159B2

Reaction notes

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