Sodium Carbonate → Tert-butyl 4-(2-chloropyrimidin-4-yl)piperazine-1-carboxylate

HRID 890563Notes

Reaction equation

HRID 890563 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16]>C(O)C>[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][N:25]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([Cl:1])[N:7]=2)[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:16])[CH3:17]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 775312,4-DichloropyrimidineHCID 143452tert-Butyl piperazine-1-carboxylate

Product 1

HCID 11197306Tert-butyl 4-(2-chloropyrimidin-4-yl)piperazine-1-carboxylateYield 77.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 2,4-dichloropyrimidine (3.00 g, 20.1 mmol) in 100 mL of ethanol was added powdered sodium carbonate (2.1 g, 20.1 mmol) and piperazine-1-carboxylic acid tert-butyl ester (3.75 g, 20.1 mmol). The reaction was heated to reflux for 5 hours, then cooled to room temperature and concentrated in vacuo. The residue was taken up in 400 mL of ethyl acetate and extracted with water (100 mL) and brine (100 mL). The organic phase was then dried over sodium sulfate, filtered, and concentrated in vacuo to a clear oil. Flash column chromatography (silica gel, gradient elution from 10% ethyl acetate-hexanes to 50% ethyl acetate-hexanes) yielded 4.63 g of the title compound (I-1a).

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 5 hours
  3. concentrationconcentrated in vacuo
  4. extractionextracted with water (100 mL) and brine (100 mL)
  5. dry with materialThe organic phase was then dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo to a clear oil
  8. washFlash column chromatography (silica gel, gradient elution from 10% ethyl acetate-hexanes to 50% ethyl acetate-hexanes)

Sources & evidence

ORD record
ord-72d9567153b944d3ac6fb6bfbe2f484e
Source dataset
uspto-grants-2006_02
Patent number
US06995159B2

Reaction notes

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