Acetic Acid → 1,1-Dimethylethyl 4-{4-[3-(methyloxy)-4-nitrophenyl]-1-piperazinyl}-1-piperidinecarboxylate

HRID 419393Notes

Reaction equation

HRID 419393 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([N:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)[CH:6]=[CH:7][C:8]=1[N+:9]([O-:11])=[O:10].[C:18]([N:25]1[CH2:30][CH2:29][C:28](=O)[CH2:27][CH2:26]1)([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19].CC(O)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([N:12]2[CH2:17][CH2:16][N:15]([CH:28]3[CH2:29][CH2:30][N:25]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:26][CH2:27]3)[CH2:14][CH2:13]2)[CH:6]=[CH:7][C:8]=1[N+:9]([O-:11])=[O:10]

Participants

6

Reactant 4

HCID 176Acetic Acid2×HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 39674091-(3-Methoxy-4-nitrophenyl)piperazineHCID 5049666Sodium triacetoxyborohydride2×

Product 1

HCID 594526201,1-Dimethylethyl 4-{4-[3-(methyloxy)-4-nitrophenyl]-1-piperazinyl}-1-piperidinecarboxylateYield 97.3%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a stirred (30 min) solution of 1-[3-(methyloxy)-4-nitrophenyl]piperazine (3.52 g, 14.9 mmol), 1-Boc-4-piperidone (5.96 g, 29.9 mmol), HOAc (24.0 mL, 1M in DCM, 24.0 mmol) and TEA (2.00 mL, 14.3 mmol) in 1,2-DCE was added in one portion sodium triacetoxyborohydride (4.82 g, 22.7 mmol). The reaction was stirred for 30 min at which time sodium triacetoxyborohydride (2.00 g, 9.40 mmol) and HOAc (10.0 mL, 1M in DCM, 10.0 mmol) was added. The reaction was stirred at rt overnight. The reaction was quenched with saturated NaHCO3 (150 mL) and extracted with DCM. The organic layer was washed with H2O, dried (MgSO4) and concentrated. Purification by flash chromatography provided the title compound of step C (6.09 g, 14.5 mmol, 97%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.20-1.32 (m, 2H), 1.37 (s, 9H), 1.74 (d, J=10.6 Hz, 2H), 2.41 (tt, J=11.0, 3.2 Hz, 1H), 2.55-2.62 (m, 4H), 2.70 (br. s., 2H), 3.36-3.44 (m, 4H), 3.88 (s, 3H), 3.94 (d, J=13.2 Hz, 2H), 6.50 (d, J=2.6 Hz, 1H), 6.57 (dd, J=9.5, 2.6 Hz, 1H), 7.86 (d, J=9.2 Hz, 1H).

Workup

  1. additionwas added
  2. customThe reaction was quenched with saturated NaHCO3 (150 mL)
  3. extractionextracted with DCM
  4. washThe organic layer was washed with H2O
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customPurification by flash chromatography

Sources & evidence

ORD record
ord-cd2aeb3cfc6447e9bc158d77503de125
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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