Diisopropylethylamine → (R)-3-(5-bromo-pyrimidin-2-ylamino)-piperidine-1-carboxylic acid tert-butyl ester

HRID 1094255Notes

Reaction equation

HRID 1094255 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1.[Br:15][C:16]1[CH:17]=[N:18][C:19](Cl)=[N:20][CH:21]=1.CCN(C(C)C)C(C)C.CC(=O)OCC.CCCCCCC>CCO.CC(=O)OCC>[C:11]([O:10][C:8]([N:4]1[CH2:5][CH2:6][CH2:7][C@@H:2]([NH:1][C:19]2[N:20]=[CH:21][C:16]([Br:15])=[CH:17][N:18]=2)[CH2:3]1)=[O:9])([CH3:14])([CH3:13])[CH3:12]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 6066655-Bromo-2-chloropyrimidineHCID 1501974tert-butyl (3R)-3-aminopiperidine-1-carboxylateHCID 21899848Ethylacetate heptane

Product 1

HCID 66639558(R)-3-(5-bromo-pyrimidin-2-ylamino)-piperidine-1-carboxylic acid tert-butyl esterYield 48%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (R)-3-amino-1-N-Boc-piperidine (920 mg) in dry EtOH (20 mL) were added successively 5-bromo-2-chloropyrimidine (957 mg), DIEA (0.86 mL). The reaction mixture was stirred at reflux for 16 hours under nitrogen. After cooling to RT, the reaction mixture was diluted with EA, washed with sat. NaHCO3, 1N NaOH. The organic extract was dried (MgSO4), filtered and concentrated to yield a crude brown-orange oil. FC (EA/n-heptane: 2/8) gave 787 mg (48%) of the title compound as a light brown solid.

Workup

  1. temperatureat reflux for 16 hours under nitrogen
  2. washwashed with sat. NaHCO3, 1N NaOH
  3. extractionThe organic extract
  4. dry with materialwas dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto yield a crude brown-orange oil

Sources & evidence

ORD record
ord-bc11a06f67ad407e8f83f67990e20913
Source dataset
uspto-grants-2012_03
Patent number
US08133901B2

Reaction notes

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