Sodium Hydroxide → HCID 59849173, compound

HRID 604267Notes

Reaction equation

HRID 604267 reaction equation
[CH3:1][N:2]1[CH2:10][C:9]2[C:4](=[C:5]([N+:18]([O-:20])=[O:19])[CH:6]=[CH:7][C:8]=2[N:11]2[CH2:16][CH2:15][C:14](=O)[CH2:13][CH2:12]2)[C:3]1=[O:21].[C:22]([O:26][C:27]([N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1)=[O:28])([CH3:25])([CH3:24])[CH3:23].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>ClCCCl>[C:22]([O:26][C:27]([N:29]1[CH2:34][CH2:33][N:32]([CH:14]2[CH2:15][CH2:16][N:11]([C:8]3[CH:7]=[CH:6][C:5]([N+:18]([O-:20])=[O:19])=[C:4]4[C:9]=3[CH2:10][N:2]([CH3:1])[C:3]4=[O:21])[CH2:12][CH2:13]2)[CH2:31][CH2:30]1)=[O:28])([CH3:25])([CH3:23])[CH3:24]

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 143452tert-Butyl piperazine-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 67037694HCID 67037694, compound

Product 1

HCID 59849173HCID 59849173, compoundYield 62.4%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of 2-methyl-7-nitro-4-(4-oxo-piperidin-1-yl)-2,3-dihydro-isoindol-1-one (4.2 g, 14.5 mmol) and piperazine-1-carboxylic acid tert-butyl ester (3.24 g, 17.4 mmol) in 1,2-dichloroethane is added sodium triacetoxy borohydride (3.69 g, 17.4 mmol) at 0° C. under nitrogen atmosphere. After the mixture is stirred at room temperature for 5 hours, 1N sodium hydroxide aqueous solution is added at 0° C. The mixture is extracted with dichloromethane and the organic layer is washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue is purified by silica gel column chromatography (AcOEt; AcOEt: MeOH=9: 1) to give 4-[1-(2-methyl-7-nitro-1-oxo-2,3-dihydro-1H-isoindol-4-yl)-piperidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (4.16 g, 62%). 1H-NMR (400 MHz, CDCl3, δ, ppm): 1.47 (s, 9H), 1.66-1.76 (m, 2H), 1.94-2.02 (m, 2H), 2.42-2.59 (m, 5H), 2.84-2.93 (m, 2H), 3.05 (s, 3H), 3.40-3.49 (m, 4H), 3.49-3.57 (m, 2H), 4.35 (s, 2H), 7.00 (d, 1H), 7.76 (d, 1H).

Workup

  1. extractionThe mixture is extracted with dichloromethane
  2. washthe organic layer is washed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue is purified by silica gel column chromatography (AcOEt; AcOEt: MeOH=9: 1)

Sources & evidence

ORD record
ord-d1e37612afa94bef9e8c05ac5d76afdf
Source dataset
uspto-grants-2011_03
Patent number
US07910585B2

Reaction notes

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