4-Bromobenzaldehyde → 1,1-Dimethylethyl (2R,6S)-4-[(4-bromophenyl)methyl]-2,6-dimethyl-1-piperazinecarboxylate

HRID 43353Notes

Reaction equation

HRID 43353 reaction equation
[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][CH:3]=1.[CH3:10][C@@H:11]1[CH2:16][NH:15][CH2:14][C@H:13]([CH3:17])[N:12]1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>ClCCCl>[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][N:15]2[CH2:16][C@H:11]([CH3:10])[N:12]([C:18]([O:20][C:21]([CH3:22])([CH3:24])[CH3:23])=[O:19])[C@H:13]([CH3:17])[CH2:14]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 707414-BromobenzaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 21021901tert-Butyl (2R,6S)-2,6-dimethylpiperazine-1-carboxylate

Product 1

HCID 252240971,1-Dimethylethyl (2R,6S)-4-[(4-bromophenyl)methyl]-2,6-dimethyl-1-piperazinecarboxylateYield 91.8%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of 4-bromobenzaldehyde (1.85 g, 10 mmol), 1,1-dimethylethyl (2R,6S)-2,6-dimethyl-1-piperazinecarboxylate (2.15 g, 10 mmol) and sodium triacetoxyborohydride (3.18 g) in 1,2-DCE (35 ml) was stirred at room temperature for 3 days. Saturated aq. NaHCO3 solution was added and the mixture stirred for 30 mins. The product was extracted into EtOAc and the extracts dried (Na2SO4) and concentrated. The residue was dissolved in DCM and treated with PS-hydrazine resin with stirring for 2 h. The resin was removed by filtration and the solvent removed in vacuo. Chromatography (0-40% EtOAc/hexane) gave the title compound (3.52 g). MS (ES): MH+ 383/385.

Workup

  1. stirringthe mixture stirred for 30 mins
  2. extractionThe product was extracted into EtOAc
  3. dry with materialthe extracts dried (Na2SO4)
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in DCM
  6. additiontreated with PS-hydrazine resin
  7. stirringwith stirring for 2 h
  8. customThe resin was removed by filtration
  9. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-758b8aff5c324789a35f03191e911f1b
Source dataset
uspto-grants-2013_09
Patent number
US08536182B2

Reaction notes

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