Hydrochloric Acid → 4-(7-Amino-2-methyl-1-oxo-2,3-dihydro-1H-isoindol-4-yl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 604268Notes

Reaction equation

HRID 604268 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:22]=[CH:21][C:20]([N+:23]([O-])=O)=[C:19]3[C:15]=2[CH2:16][N:17]([CH3:27])[C:18]3=[O:26])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[OH-].[Na+]>C(O)C.[Fe]>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][N:11]([C:14]2[CH:22]=[CH:21][C:20]([NH2:23])=[C:19]3[C:15]=2[CH2:16][N:17]([CH3:27])[C:18]3=[O:26])[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 598491954-(2-methyl-7-nitro-1-oxo-2,3-dihydro-1H-isoindol-4-yl)-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 598491864-(7-Amino-2-methyl-1-oxo-2,3-dihydro-1H-isoindol-4-yl)-piperazine-1-carboxylic acid tert-butyl esterYield 101%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 4-(2-methyl-7-nitro-1-oxo-2,3-dihydro-1H-isoindol-4-yl)-piperazine-1-carboxylic acid tert-butyl ester (5.37 g, 14 mmol) in ethanol (200 mL), iron powder (3.98 g, 70 mmol) and 1N hydrogen chloride (28 mL) are added and the mixture is stirred at 60° C. for 2 hours. The mixture is cooled to room temperature, and then 1N sodium hydroxide (28 mL) is added. After removing insoluble material by filtration, the mixture is concentrated. The residue is extracted twice with dichloromethane. The organic layer is successively washed with water and brine, dried over magnesium sulfate, and evaporated in vacuo to afford 4-(7-Amino-2-methyl-1-oxo-2,3-dihydro-1H-isoindol-4-yl)-piperazine-1-carboxylic acid tert-butyl ester (4.9 g) as pale green amorphous solids in 99% yield. Rf=0.18 (Hexane/AcOEt=111). 1H-NMR (400 MHz, CDCl3, δ, ppm): 1.49 (s, 9H), 2.85 (t, 4H), 3.13 (s, 3H), 3.54 (t, 4H), 4.28 (s, 2H), 5.03 (s, 2H), 6.56 (d, 1H), 6.96 (d, 1H).

Workup

  1. temperatureThe mixture is cooled to room temperature
  2. customAfter removing insoluble material
  3. filtrationby filtration
  4. concentrationthe mixture is concentrated
  5. extractionThe residue is extracted twice with dichloromethane
  6. washThe organic layer is successively washed with water and brine
  7. dry with materialdried over magnesium sulfate
  8. customevaporated in vacuo

Sources & evidence

ORD record
ord-46ee7f3081cf4b148f5a4eb4b9e5c78a
Source dataset
uspto-grants-2011_03
Patent number
US07910585B2

Reaction notes

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