Ethyl bromoacetate → HCID 68512513, compound

HRID 1513003Notes

Reaction equation

HRID 1513003 reaction equation
[Cl:1][C:2]1[C:3]([N:23]2[C:31](=[O:32])[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[C:24]2=[O:33])=[CH:4][C:5]([S:9]([N:12]2[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=3[CH2:16][CH2:15][CH2:14][CH2:13]2)(=[O:11])=[O:10])=[C:6]([OH:8])[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:41][C:42]([O:44][CH2:45][CH3:46])=[O:43]>CN(C)C=O.C(OCC)(=O)C>[Cl:1][C:2]1[C:3]([N:23]2[C:24](=[O:33])[C:25]3[C:30](=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:31]2=[O:32])=[CH:4][C:5]([S:9]([N:12]2[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=3[CH2:16][CH2:15][CH2:14][CH2:13]2)(=[O:10])=[O:11])=[C:6]([CH:7]=1)[O:8][CH2:41][C:42]([O:44][CH2:45][CH3:46])=[O:43]

Participants

6

Reactant 3

HCID 7748Ethyl bromoacetateHCID 11430Potassium CarbonateHCID 59309908HCID 59309908, compound

Product 1

HCID 68512513HCID 68512513, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 5-chloro-2-(2,3,4,5-tetrahydro-1H-1-benzoazepin-1-yl-sulfonyl)-4-(1,3-dioxo-1,3-dihydroisoindol-2-yl)phenol (0.26 g) and potassium carbonate (0.11 g) in N,N-dimethylformamide (3 mL) was added ethyl bromoacetate (0.078 mL), and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with ethyl acetate, and the resulting mixture was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=9/1−1/9) to give ethyl 2-[5-chloro-2-(2,3,4,5-tetrahydro-1H-1-benzoazepin-1-yl-sulfonyl)-4-(1,3-dioxo-1,3-dihydroisoindol-2-yl)phenoxy]acetate (0.29 g). To this material were added tetrahydrofuran (10 mL), methanol (5 mL), water (5 mL) and lithium hydroxide monohydrate (0.21 g), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into 1 mol/L hydrochloric acid, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was dissolved in tetrahydrofuran (5 mL). To the solution was added 1,1′-carbonyldiimidazole (0.16 g), and the mixture was stirred at room temperature for 30 minutes. To the reaction mixture was added methylamine (40% methanol solution, 2.5 mL), and the mixture was stirred at room temperature for 5 hours, and then stirred at 50° C. for 1 hour. The reaction mixture was poured into 2 mol/L hydrochloric acid, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=1/1−ethyl acetate) to give the title compound (0.14 g).

Workup

  1. washthe resulting mixture was washed with water and brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. customThe solvent was removed under reduced pressure
  4. customthe residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=9/1−1/9)

Sources & evidence

ORD record
ord-3b921a6325c8458fada14183c419cb75
Source dataset
uspto-grants-2012_07
Patent number
US08217069B2

Reaction notes

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