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

HRID 1193348Notes

Reaction equation

HRID 1193348 reaction equation
[CH3:1][N:2]([CH2:10]C1CCNCC1)[C:3](=[O:9])[O:4][C:5]([CH3:8])([CH3:7])[CH3:6].Cl.Cl[C:19]1C=C[N:22]=[CH:21][N:20]=1.[CH3:25][CH2:26][N:27]([CH:31]([CH3:33])C)[CH:28]([CH3:30])C>CC(O)C.C(OCC)(=O)C.C(=O)([O-])O.[Na+]>[CH3:10][N:2]([CH:1]1[CH2:25][CH2:26][N:27]([C:28]2[CH:30]=[CH:19][N:20]=[CH:21][N:22]=2)[CH2:31][CH2:33]1)[C:3](=[O:9])[O:4][C:5]([CH3:6])([CH3:7])[CH3:8]

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 219225564-Chloropyrimidine hydrochlorideHCID 23004743tert-butyl N-methyl-N-(piperidin-4-ylmethyl)carbamate

Product 1

HCID 66805510tert-Butyl methyl(1-(pyrimidin-4-yl)piperidin-4-yl)carbamateYield 78%

Reagents, catalysts & solvents 3

HCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

tert-Butyl methyl(piperidin-4-ylmethyl)carbamate (4.67 mmol, 1.0 eq) and 4-chloropyrimidine hydrochloride (14.0 mmol, 3.0 eq) were dissolved in 2-propanol (18 ml) and DIPEA (23.33 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 washed 1× with sat. NaCl solution, dried over magnesium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel, ethyl acetate:ethanol 10:1+ammonia solution). Yield: 78%

Workup

  1. customthe phases were separated
  2. washThe aqueous phase was washed with ethyl acetate
  3. washThe combined organic phases were washed 1× with sat. NaCl solution
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by column chromatography (silica gel, ethyl acetate:ethanol 10:1+ammonia solution)

Sources & evidence

ORD record
ord-591f2dab44124e49884ff13bf94600a1
Source dataset
uspto-grants-2014_03
Patent number
US08680159B2

Reaction notes

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