Water → 5-fluoro-2-(2,3,4,5-tetrahydro-1H-1-benzoazepin-1-ylsulfonyl)-4-(1,3-dioxo-1,3-dihydroisoindol-2-yl)anisole

HRID 1512996Notes

Reaction equation

HRID 1512996 reaction equation
[NH:1]1[CH2:7][CH2:6][CH2:5][CH2:4][C:3]2[CH:8]=[CH:9][CH:10]=[CH:11][C:2]1=2.C(N(CC)CC)C.[F:19][C:20]1[C:25]([N:26]2[C:34](=[O:35])[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:27]2=[O:36])=[CH:24][C:23]([S:37](Cl)(=[O:39])=[O:38])=[C:22]([O:41][CH3:42])[CH:21]=1.O>CN(C)C1C=CN=CC=1.C(Cl)Cl>[F:19][C:20]1[C:25]([N:26]2[C:34](=[O:35])[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:27]2=[O:36])=[CH:24][C:23]([S:37]([N:1]2[C:2]3[CH:11]=[CH:10][CH:9]=[CH:8][C:3]=3[CH2:4][CH2:5][CH2:6][CH2:7]2)(=[O:38])=[O:39])=[C:22]([O:41][CH3:42])[CH:21]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 5765032,3,4,5-tetrahydro-1H-1-benzazepineHCID 593097434-Fluoro-5-(1,3-dioxo-1,3-dihydroisoindol-2-yl)-2-methoxybenzenesulfonyl chloride

Product 1

HCID 685144615-fluoro-2-(2,3,4,5-tetrahydro-1H-1-benzoazepin-1-ylsulfonyl)-4-(1,3-dioxo-1,3-dihydroisoindol-2-yl)anisoleYield 87.7%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2,3,4,5-tetrahydro-1H-benzo[B]azepine (0.24 g), triethylamine (0.23 mL) and 4-dimethylaminopyridine (17 mg) in methylene chloride (8 mL) was added 4-fluoro-5-(1,3-dioxo-1,3-dihydroisoindol-2-yl)-2-methoxybenzenesulfonyl chloride (0.5 g), and the mixture was stirred at room temperature for 5 hours. The reaction mixture was poured into water, and the resulting mixture was extracted with ethyl acetate. The extract was washed with 1 mol/L hydrochloric acid, water and brine successively, and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure to give 5-fluoro-2-(2,3,4,5-tetrahydro-1H-1-benzoazepin-1-ylsulfonyl)-4-(1,3-dioxo-1,3-dihydroisoindol-2-yl)anisole (0.57 g). This material was dissolved in tetrahydrofuran (11 mL). To the solution was added hydrazine monohydrate (0.29 mL), and the mixture was heated at reflux for 2 hours. The reaction mixture was cooled to room temperature, and diluted with ethyl acetate. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane−n-hexane/ethyl acetate=2/3) to give the title compound (0.32 g).

Workup

  1. extractionthe resulting mixture was extracted with ethyl acetate
  2. washThe extract was washed with 1 mol/L hydrochloric acid, water and brine successively
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-e05e158957704cc8beac31104cd218d9
Source dataset
uspto-grants-2012_07
Patent number
US08217069B2

Reaction notes

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