Water → (S)-3-(tert-Butoxycarbonylamino)-1-(4-methoxy-5-isoquinolinesulfonyl)pyrrolidine

HRID 2425388Notes

Reaction equation

HRID 2425388 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:13][CH2:12][N:11]([S:14]([C:17]2[C:18]3[C:19](Br)=[CH:20][N:21]=[CH:22][C:23]=3[CH:24]=[CH:25][CH:26]=2)(=[O:16])=[O:15])[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C[O-].[Na+].O.[C:32](OCC)(=[O:34])C>CO.N1C=CC=CC=1.[Cu](I)I>[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:13][CH2:12][N:11]([S:14]([C:17]2[C:18]3[C:19]([O:34][CH3:32])=[CH:20][N:21]=[CH:22][C:23]=3[CH:24]=[CH:25][CH:26]=2)(=[O:16])=[O:15])[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 10942334Sodium MethoxideHCID 67242852(S)-3-(tert-Butoxycarbonylamino)-1-(4-bromo-5-isoquinolinesulfonyl)pyrrolidine

Product 1

HCID 67243480(S)-3-(tert-Butoxycarbonylamino)-1-(4-methoxy-5-isoquinolinesulfonyl)pyrrolidine

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 887MethanolSolvent2×HCID 1049PyridineSolvent

Procedure

A solution of Intermediate 1a (337 mg) obtained in Example 1-1, Step A in methanol (2.7 ml) and pyridine (2.7 ml) was added with a solution of 28% sodium methylate (847 mg) in methanol, and then with copper iodide (70 mg), and the mixture was stirred at 65° C. for 30 hours. The reaction mixture was cooled to room temperature, and added with water (30 ml) and ethyl acetate (30 ml), and the insoluble solids were removed by filtration through Celite. The organic layer of the filtrate was separated, and the aqueous layer was extracted 3 times with ethyl acetate (20 ml for each time). The combined organic layer was washed 3 times with saturated brine (30 ml for each time), and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel chromatography (chloroform:methanol=30:1) to obtain the title compound (98 mg).

Workup

  1. customthe insoluble solids were removed by filtration through Celite
  2. customThe organic layer of the filtrate was separated
  3. extractionthe aqueous layer was extracted 3 times with ethyl acetate (20 ml for each time)
  4. washThe combined organic layer was washed 3 times with saturated brine (30 ml for each time), and
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. customthe residue was purified by silica gel chromatography (chloroform:methanol=30:1)

Sources & evidence

ORD record
ord-c8efa55e53dd4f8097978b5c12731a96
Source dataset
uspto-grants-2011_06
Patent number
US07964613B2

Reaction notes

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