tert-Butyl piperazine-1-carboxylate → HCID 69156702, compound

HRID 967043Notes

Reaction equation

HRID 967043 reaction equation
[CH3:1][C:2]1[C:9]([CH3:10])=[C:8]([O:11][CH3:12])[CH:7]=[CH:6][C:3]=1[CH:4]=O.[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].N1C2C=CC=C[C:29]=2N=N1.C[Mg]Br>C(O)C>[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][N:23]([CH:4]([C:3]2[CH:6]=[CH:7][C:8]([O:11][CH3:12])=[C:9]([CH3:10])[C:2]=2[CH3:1])[CH3:29])[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:14])[CH3:15]

Participants

6

Reactant 4

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 5960582,3-Dimethyl-p-anisaldehydeHCID 178418385HCID 178418385, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 69156702HCID 69156702, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 2,3-dimethyl 4-methoxy benzaldehyde (1 g, 3.05 mmol), 1 equivalent of piperazine-1-carboxylic acid tert-butyl ester (0.57 g, 3.05 mmol), 1 equivalent of benzotriazole in ethanol was stirred at room temperature for 30 minutes. The solvent was removed and the reaction was dried under vacuum. The reaction mixture was then dissolved in anhydrous THF(20 ml) under N2 at −78° C. Then 3 equivalents (3.05 ml) of methyl magnesium bromide (3M in THF) was added to the solution slowly. The reaction mixture was kept at this temperature for 2 hours and warmed up to room temperature for overnight. The mixture was washed with 2N NaOH and water and extracted with ethyl acetate (2×30 ml). The combined organic layers were dried over MgSO4. After removal of organic solvent, the residue was purified by a flash column on silica gel eluted with 1:1 EtOAC:Hexane first, then with 10% MeOH(NH3) in dichloromethane. 4-[1-(4-methoxy-2,3-dimethyl-phenyl)-ethyl]-piperazine-1-carboxylic acid tert-butyl ester was obtained as a yellow oil (0.59 g, 56%). Analysis H1 NMR (400 MHz, CDCl3): 7.21 (1H, d), 6.68 (1H, d), 3.8 (3H, s), 3.58 (1H, q), 3.38 (3H, m), 2.45 (2H, m), 2.37 (2H, m), 2.24 (3H, s), 2.18 (3H, s), 1.43 (9H, s), 1.24 (3H, d). MS (LC-MS): Calculated for C20H32N2O3 348.48, found 349.29 (M+).

Workup

  1. customThe solvent was removed
  2. customthe reaction was dried under vacuum
  3. dissolutionThe reaction mixture was then dissolved in anhydrous THF(20 ml) under N2 at −78° C
  4. waitThe reaction mixture was kept at this temperature for 2 hours
  5. temperaturewarmed up to room temperature for overnight
  6. washThe mixture was washed with 2N NaOH and water
  7. extractionextracted with ethyl acetate (2×30 ml)
  8. dry with materialThe combined organic layers were dried over MgSO4
  9. customAfter removal of organic solvent
  10. customthe residue was purified by a flash column on silica gel
  11. washeluted with 1:1 EtOAC

Sources & evidence

ORD record
ord-1bcc8c7f08fa43dab7af95018ef354bb
Source dataset
uspto-grants-2005_10
Patent number
US06953801B2

Reaction notes

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