Triethylamine → tert-Butyl 4-(4-chloropyrimidin-2-yl)piperazine-1-carboxylate

HRID 1465467Notes

Reaction equation

HRID 1465467 reaction equation
Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[CH:4][N:3]=1.[N:9]1([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1.C(N(CC)CC)C>CC(O)C>[Cl:8][C:6]1[N:5]=[C:4]([N:12]2[CH2:11][CH2:10][N:9]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:14][CH2:13]2)[N:3]=[CH:2][CH:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 709434,6-DichloropyrimidineHCID 143452tert-Butyl piperazine-1-carboxylate

Product 1

HCID 46738270tert-Butyl 4-(4-chloropyrimidin-2-yl)piperazine-1-carboxylateYield 95%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

To a solution (60 ml) of 4,6-dichloropyrimidine (2.00 g, 13.4 mmol) and tert-butyl piperazine-1-carboxylate (3.00 g, 16.1 mmol) in 2-propanol was added triethylamine (4.7 ml, 33.6 mmol), and the mixture was heated under reflux for 2 hrs. The mixture was concentrated under reduced pressure, dichloromethane was added to the residue, and the mixture was washed with water. The aqueous layer was extracted with dichloromethane, and the combined organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:2) to give tert-butyl 4-(6-chloropyrimidin-2-yl)piperazine-1-carboxylate (3.80 g, yield 95%) as a white solid.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 2 hrs
  3. concentrationThe mixture was concentrated under reduced pressure, dichloromethane
  4. additionwas added to the residue
  5. washthe mixture was washed with water
  6. extractionThe aqueous layer was extracted with dichloromethane
  7. dry with materialthe combined organic layer was dried over anhydrous sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:2)

Sources & evidence

ORD record
ord-1d842dd940ed4b08a93ae1f39cf56f70
Source dataset
uspto-grants-2015_04
Patent number
US08999989B2

Reaction notes

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