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

HRID 875004Notes

Reaction equation

HRID 875004 reaction equation
Cl[C:2]1[N:7]=[C:6]([Cl:8])[CH:5]=[CH:4][N:3]=1.[C:9]([N:16]1[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1)([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10].C([O-])(O)=O.[Na+]>CCO>[Cl:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([N:19]2[CH2:18][CH2:17][N:16]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:21][CH2:20]2)[N:7]=1

Participants

5

Reactant 3

HCID 775312,4-DichloropyrimidineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 516892Sodium Bicarbonate

Product 1

HCID 46738270tert-Butyl 4-(4-chloropyrimidin-2-yl)piperazine-1-carboxylateYield 35%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

2,4-Dichloropyrimidine (5.0 g, 33.56 mmol) and 1-Boc-piperazine (6.25 g, 33.56 mmol) were dissolved in EtOH (40 mL). NaHCO3 (5.07 g, 60.41 mmol) was added and the reaction mixture was heated to reflux for 1.5 h, cooled to room temperature, and concentrated under reduced pressure. The mixture was diluted with CH2Cl2 and the organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica 60-120 mesh, eluent 5% MeOH in CH2Cl2) to get tert-butyl 4-(4-chloropyrimidin-2-yl)piperazine-1-carboxylate (3.5 g, yield 35%). 1H NMR (400 MHz, CDCl3) δ 8.07-8.05 (d, J=6.0 Hz, 1H), 6.40-6.39 (d, J=6.3 Hz, 1H), 3.65 (m, 4H), 3.54-3.51 (m, 4H), 1.48 (s, 9H). MS (ESI) m/z: Calculated for C13H19ClN4O2: 298.12. found: 299.2 (M+H)+

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureto reflux for 1.5 h
  3. concentrationconcentrated under reduced pressure
  4. additionThe mixture was diluted with CH2Cl2
  5. washthe organic layer was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by column chromatography (silica 60-120 mesh, eluent 5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-96829d5b88074e26bb2c921e3f3a258f
Source dataset
uspto-grants-2015_03
Patent number
US08981084B2

Reaction notes

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