Potassium Carbonate → Tert-butyl 4-(4-formylphenyl)piperazine-1-carboxylate

HRID 2120076Notes

Reaction equation

HRID 2120076 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].F[C:15]1[CH:22]=[CH:21][C:18]([CH:19]=[O:20])=[CH:17][CH:16]=1.C([O-])([O-])=O.[K+].[K+]>N1C=CC=CC=1>[CH:19]([C:18]1[CH:21]=[CH:22][C:15]([N:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9][CH2:10]2)=[CH:16][CH:17]=1)=[O:20]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 680234-FluorobenzaldehydeHCID 143452tert-Butyl piperazine-1-carboxylate

Product 1

HCID 2795509Tert-butyl 4-(4-formylphenyl)piperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

1-(t-Butoxycarbonyl)piperazine (1.86 g, 10 mmol), p-fluorobenzaldehyde 27 (1.24 g, 10 mmol), and K2CO3 (1.74 g, 11 mmol) in dry pyridine (10 mL) are stirred at reflux under a nitrogen atmosphere for 24 h. Most of the solvent is removed under vacuum and the residue is partitioned between EtOAc (150 mL) and water (100 mL). The aqueous layer is washed with EtOAc (2×50 mL) and the combined organic layers are sequentially washed with 3% aq. citric acid (2×100 mL), water (100 mL), brine (100 mL), and dried (MgSO4). The solvent is removed under vacuum and the residue washed with hexanes and dried under vacuum. The product can be used as such, or further purified by silica gel column chromatography (dichloromethane-MeOH gradient).

Workup

  1. temperatureat reflux under a nitrogen atmosphere for 24 h
  2. customMost of the solvent is removed under vacuum
  3. customthe residue is partitioned between EtOAc (150 mL) and water (100 mL)
  4. washThe aqueous layer is washed with EtOAc (2×50 mL)
  5. washthe combined organic layers are sequentially washed with 3% aq. citric acid (2×100 mL), water (100 mL), brine (100 mL)
  6. dry with materialdried (MgSO4)
  7. customThe solvent is removed under vacuum
  8. washthe residue washed with hexanes
  9. customdried under vacuum
  10. customfurther purified by silica gel column chromatography (dichloromethane-MeOH gradient)

Sources & evidence

ORD record
ord-663a39e12a7742f5b80085dff4892ff7
Source dataset
uspto-grants-2004_02
Patent number
US06689769B2

Reaction notes

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