4-Nitrobenzaldehyde → (3R,5S)-1-[(4-Nitrophenyl)methyl]-3,5-dimethylpiperazine

HRID 2424631Notes

Reaction equation

HRID 2424631 reaction equation
[N+:1]([C:4]1[CH:11]=[CH:10][C:7]([CH:8]=O)=[CH:6][CH:5]=1)([O-:3])=[O:2].[CH3:12][C@@H:13]1[CH2:18][NH:17][CH2:16][C@H:15]([CH3:19])[NH:14]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C(Cl)Cl>[N+:1]([C:4]1[CH:11]=[CH:10][C:7]([CH2:8][N:17]2[CH2:16][C@H:15]([CH3:19])[NH:14][C@H:13]([CH3:12])[CH2:18]2)=[CH:6][CH:5]=1)([O-:3])=[O:2]

Participants

6

Reactant 3

HCID 5414-NitrobenzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 6950261rel-(2R,6S)-2,6-dimethylpiperazine

Product 1

HCID 59262210(3R,5S)-1-[(4-Nitrophenyl)methyl]-3,5-dimethylpiperazineYield 39.2%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 4-nitrobenzaldehyde (6.612 g, 43.8 mmol) and (2R,6S)-2,6-dimethylpiperazine (5 g, 43.8 mmol) in 1,2-DCE (100 mL) was stirred at room temperature for 2 h. Sodium tri(acetoxy)borohydride (13.92 g, 65.7 mmol) was added and the reaction was stirred at room temperature over-weekend. The reaction mixture was diluted with DCM and washed with saturated aqueous NaHCO3 solution. The aqueous wash was extracted with 10% MeOH/DCM and the combined organics were dried and concentrated. Column chromatography eluting with 0-10% MeOH/DCM gave the title compound as a cream solid (4.278 g). δH (CDCl3, 400 MHz) 8.18 (2H, d), 7.51 (2H, d), 3.57 (2H, s), 2.97 (2H, m), 2.72 (2H, m), 1.72 (2H, m), 1.06 (6H, d). MS (ES+): MH+ 250.2.

Workup

  1. stirringthe reaction was stirred at room temperature over-weekend
  2. washwashed with saturated aqueous NaHCO3 solution
  3. washThe aqueous wash
  4. extractionwas extracted with 10% MeOH/DCM
  5. customthe combined organics were dried
  6. concentrationconcentrated
  7. washColumn chromatography eluting with 0-10% MeOH/DCM

Sources & evidence

ORD record
ord-429f271f18754f0ab5a3677a0b751574
Source dataset
uspto-grants-2011_06
Patent number
US07964597B2

Reaction notes

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