4-Nitrobenzaldehyde → 1,1-Dimethylethyl (2S)-2-methyl-4-[(4-nitrophenyl)methyl]-1-piperazinecarboxylate

HRID 883777Notes

Reaction equation

HRID 883777 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].Cl.[CH3:13][C@H:14]1[CH2:19][NH:18][CH2:17][CH2:16][N:15]1[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21].C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>ClCCCl>[CH3:13][C@H:14]1[CH2:19][N:18]([CH2:8][C:7]2[CH:10]=[CH:11][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=2)[CH2:17][CH2:16][N:15]1[C:20]([O:22][C:23]([CH3:24])([CH3:26])[CH3:25])=[O:21]

Participants

7

Reactant 5

HCID 5414-NitrobenzaldehydeHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 45072182(S)-tert-butyl 2-methylpiperazine-1-carboxylate hydrochloride

Product 1

HCID 592622041,1-Dimethylethyl (2S)-2-methyl-4-[(4-nitrophenyl)methyl]-1-piperazinecarboxylate

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of 4-nitrobenzaldehyde (15.1 g, 0.1 mol), 1,1-dimethylethyl (2S)-2-methyl-1-piperazinecarboxylate hydrochloride (21.3 g, 0.09 mol), triethylamine (15 ml, 0.108 mol) and sodium tri(acetoxy)borohydride (42.4 g, 0.2 mol) in 1,2-DCE (500 ml) was stirred at room temperature overnight. Saturated aqueous NaHCO3 solution (200 ml) was added and the mixture stirred for 20-30 minutes. The phases were separated and the aqueous phase was washed with DCM. The combined organics were washed with brine, dried and concentrated. Column chromatography eluting with 0-20% EtOAc/hexane gave the title compound as a yellow oil which crystallized on standing (25.61 g). δH (CDCl3, 400 MHz) 8.19 (2H, d), 7.53 (2H, d), 4.21 (1H, br.s), 3.83 (1H, d), 3.62 (1H, d), 3.50 (1H, d), 3.13 (1H, td), 2.74 (1H, m), 2.54 (1H, m), 2.20 (1H, dd), 2.08 (1H, m), 1.46 (9H, s), 1.25 (3H, d).

Workup

  1. stirringthe mixture stirred for 20-30 minutes
  2. customThe phases were separated
  3. washthe aqueous phase was washed with DCM
  4. washThe combined organics were washed with brine
  5. customdried
  6. concentrationconcentrated
  7. washColumn chromatography eluting with 0-20% EtOAc/hexane

Sources & evidence

ORD record
ord-27165ce303824fdc8ef37880e890a587
Source dataset
uspto-grants-2012_08
Patent number
US08236953B2

Reaction notes

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