tert-butyl (3R)-3-aminopiperidine-1-carboxylate → (R)-tert-Butyl 3-(2-chloro-5-fluoro-6-morpholinopyrimidin-4-ylamino)piperidine-1-carboxylate

HRID 573995Notes

Reaction equation

HRID 573995 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.[Cl:15][C:16]1[N:21]=[C:20]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[C:19]([F:28])=[C:18](Cl)[N:17]=1>C(O)C>[Cl:15][C:16]1[N:17]=[C:18]([NH:1][C@@H:2]2[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]2)[C:19]([F:28])=[C:20]([N:22]2[CH2:23][CH2:24][O:25][CH2:26][CH2:27]2)[N:21]=1

Participants

4

Reactant 2

HCID 1501974tert-butyl (3R)-3-aminopiperidine-1-carboxylateHCID 866441264-(2,6-Dichloro-5-fluoropyrimidin-4-yl)morpholine

Product 1

HCID 90409880(R)-tert-Butyl 3-(2-chloro-5-fluoro-6-morpholinopyrimidin-4-ylamino)piperidine-1-carboxylateYield 48.7%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

(R)-tert-Butyl 3-aminopiperidine-1-carboxylate (1.60 g, 7.99 mmol) was added to a solution of 4-(2,6-dichloro-5-fluoropyrimidin-4-yl)morpholine (Preparation 11a, 1.01 g, 4.00 mmol) in ethanol (48 mL) and the resulting mixture was stirred and heated to reflux for 3 days. After cooling to ambient temperature, the solvent was evaporated under reduced pressure and the residue was partitioned between water and methylene chloride. The organic layer was separated, washed with water, dried (MgSO4) and the solvent evaporated under reduced pressure. The residue was purified by flash chromatography (0-100% ethyl acetate in hexanes) to give the title compound (0.810 g, 47%) as a white foam.

Workup

  1. temperatureheated
  2. temperatureto reflux for 3 days
  3. customthe solvent was evaporated under reduced pressure
  4. customthe residue was partitioned between water and methylene chloride
  5. customThe organic layer was separated
  6. washwashed with water
  7. dry with materialdried (MgSO4)
  8. customthe solvent evaporated under reduced pressure
  9. customThe residue was purified by flash chromatography (0-100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-481a68890fe54af89ae200b3fe852551
Source dataset
uspto-grants-2015_05
Patent number
US09034311B2

Reaction notes

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