Pyridine → Tert-butyl 4-(4-acetoxybenzoyl)piperazine-1-carboxylate

HRID 856107Notes

Reaction equation

HRID 856107 reaction equation
[C:1]([O:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=O)=[CH:7][CH:6]=1)(=[O:3])[CH3:2].S(Cl)(Cl)=O.[N:18]1([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1.N1C=CC=CC=1>C(Cl)Cl.CN(C=O)C>[C:1]([O:4][C:5]1[CH:6]=[CH:7][C:8]([C:9]([N:21]2[CH2:20][CH2:19][N:18]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:23][CH2:22]2)=[O:11])=[CH:12][CH:13]=1)(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 1049PyridineHCID 16865Benzoic acid, 4-(acetyloxy)-HCID 24386Thionyl ChlorideHCID 143452tert-Butyl piperazine-1-carboxylate

Product 1

HCID 23081258Tert-butyl 4-(4-acetoxybenzoyl)piperazine-1-carboxylateYield 95.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent3×

Procedure

p-Acetoxybenzoic acid (11 g, 61.1 mmol) was dissolved in methylene chloride (100 ml), to which DMF (3 drops) and thionyl chloride (5.54 ml, 76.3 mmol) were added, and the mixture was heated under reflux for 2 hours. The mixture was cooled in an ice-bath, to which a solution of tert-butyl piperazine-1-carboxylate (10.3 g, 55.5 mmol) and pyridine (12 ml, 0.15 mol) in methylene chloride (100 ml) was added dropwise, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with methylene chloride, and the mixture was washed with water, 10% hydrochloric acid, saturated sodium hydrogencarbonate aqueous solution and brine, dried over magnesium sulfate, and then filtered. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (methylene chloride/ethyl acetate=20/1) to afford tert-butyl 4-(4-acetoxybenzoyl)piperazine-1-carboxylate (18.5 g, yield 87%) as a colorless crystalline powder.

Workup

  1. additionwere added
  2. temperaturethe mixture was heated
  3. temperatureunder reflux for 2 hours
  4. additionwas added dropwise
  5. washthe mixture was washed with water, 10% hydrochloric acid, saturated sodium hydrogencarbonate aqueous solution and brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (methylene chloride/ethyl acetate=20/1)

Sources & evidence

ORD record
ord-cea2c6a86a6440738d3a9a6abc023fbc
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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