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

HRID 890566Notes

Reaction equation

HRID 890566 reaction equation
Cl[C:2]1[N:7]=[C:6]([Cl:8])[CH:5]=[CH:4][N:3]=1.[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][N:19](C)[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10]>C1(C)C=CC=CC=1>[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][N:19]([C:2]2[N:7]=[C:6]([Cl:8])[CH:5]=[CH:4][N:3]=2)[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:10])[CH3:11]

Participants

4

Reactant 2

HCID 775312,4-DichloropyrimidineHCID 114013941-Boc-4-methylpiperazine

Product 1

HCID 46738270tert-Butyl 4-(4-chloropyrimidin-2-yl)piperazine-1-carboxylateYield 56.9%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a suspension of 2,4-dichloropyrimidine (1.00 g, 6.71 mmol) in 13.4 mL of toluene was added 4-methyl-piperazine-1-carboxylic acid tert-butyl ester (1.34 g, 6.71 mmol). The reaction was heated to reflux overnight, then cooled to room temperature and concentrated in vacuo. The residue was taken up in 20 mL of water and extracted with ethyl acetate (2×40 mL). The combined organic layers were washed with brine (25 mL), then dried over sodium sulfate, filtered, and concentrated in vacuo to an off-white solid. Flash column chromatography (silica gel, gradient elution from 5% ethyl acetate-hexanes to 20% ethyl acetate-hexanes) yielded 1.14 g of the title compound (I-2a).

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux overnight
  3. concentrationconcentrated in vacuo
  4. extractionextracted with ethyl acetate (2×40 mL)
  5. washThe combined organic layers were washed with brine (25 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo to an off-white solid
  9. washFlash column chromatography (silica gel, gradient elution from 5% ethyl acetate-hexanes to 20% ethyl acetate-hexanes)

Sources & evidence

ORD record
ord-ecaa0ddc47c040cf8f7aea32f78f69bb
Source dataset
uspto-grants-2006_02
Patent number
US06995159B2

Reaction notes

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