Phthalimide potassium salt → HCID 68854787, compound

HRID 1986214Notes

Reaction equation

HRID 1986214 reaction equation
[C:1]1(=[O:11])[NH:5][C:4](=[O:6])[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]12.[K].[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH2:23][CH:22]([CH2:26][CH2:27][CH2:28]OS(C)(=O)=O)[CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14]>CN(C=O)C>[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH2:23][CH:22]([CH2:26][CH2:27][CH2:28][N:5]2[C:1](=[O:11])[C:2]3[C:3](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:4]2=[O:6])[CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14]

Participants

4

Reactant 2

HCID 24194345Phthalimide potassium saltHCID 87602782HCID 87602782, compound

Product 1

HCID 68854787HCID 68854787, compoundYield 94.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
55 °C

Procedure

Potassium phthalimide (7.79 g, 42.1 mmol) is added to a stirred solution of racemic 3-(3-methanesulfonyloxypropyl)-piperidine-1-carboxylic acid tert-butyl ester (9.00 g, 28.0 mmol) in DMF (60 mL). The mixture is allowed to stir at 55° C. for 16 hours. At room temperature, the mixture is concentrated, the oil is diluted in ethyl acetate (50 mL), and the solution is washed with water (50 mL). The organic layer is concentrated and the crude product is chromatographed on silica gel, eluting with ethyl acetate in hexane 0-25%, to give 3-[3-(1,3-dioxo-1,3-dihydroisoindol-2-yl)-propyl]-piperidine-1-carboxylic acid tert-butyl ester (9.84 g, 94% yield). A stirred solution of this intermediate (9.00 g, 24.2 mmol) in ethanol (400 mL) is treated with hydrazine (4.65 g, 145 mmol). The mixture is heated at 50° C. for 16 hours to form a white suspension. At room temperature the suspension is quickly filtered and the filtrate is concentrated to give the oil containing a small amount of white solid. This mixture is diluted in ethanol (10 mL and diethyl ether (50 mL), filtered, and concentrated to provide the title compound as an oil (5.0 g, 85% yield).

Workup

  1. concentrationAt room temperature, the mixture is concentrated
  2. additionthe oil is diluted in ethyl acetate (50 mL)
  3. washthe solution is washed with water (50 mL)
  4. concentrationThe organic layer is concentrated
  5. customthe crude product is chromatographed on silica gel
  6. washeluting with ethyl acetate in hexane 0-25%

Sources & evidence

ORD record
ord-9ddacd42dfd84b90b81382dccacca224
Source dataset
uspto-grants-2009_06
Patent number
US07547691B2

Reaction notes

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