Dimethylformamide → methyl 4-(8-bromo-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamido)-3-chlorobenzoate

HRID 84490Notes

Reaction equation

HRID 84490 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[NH:12][CH3:13])[C:5]([O:7][CH3:8])=[O:6].CN(C)C=O.[H-].[Na+].[Br:21][C:22]1[CH:23]=[CH:24][C:25]2[C:31]3[S:32][C:33]([C:35](Cl)=[O:36])=[CH:34][C:30]=3[CH2:29][CH2:28][O:27][C:26]=2[CH:38]=1>>[Br:21][C:22]1[CH:23]=[CH:24][C:25]2[C:31]3[S:32][C:33]([C:35]([N:12]([C:11]4[CH:10]=[CH:9][C:4]([C:5]([O:7][CH3:8])=[O:6])=[CH:3][C:2]=4[Cl:1])[CH3:13])=[O:36])=[CH:34][C:30]=3[CH2:29][CH2:28][O:27][C:26]=2[CH:38]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 23085096Methyl 3-chloro-4-(methylamino)benzoateHCID 579004128-Bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carbonyl chloride

Product 1

HCID 56834273methyl 4-(8-bromo-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamido)-3-chlorobenzoateYield 65%

Procedure

To a solution containing methyl 3-chloro-4-(methylamino)benzoate (0.184 g, 0.922 mmol) in N,N-dimethylformamide (11.0 mL, 142 mmol) was added sodium hydride (0.0369 g, 0.922 mmol). The mixture was stirred at room temperature 30 min then 8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carbonyl chloride (0.288 g, 0.838 mmol) was added. The reaction mixture was stirred for 16 hr. The reaction mixture was quenched with sat. NH4Cl, extracted with DCM (2×). The combined organics were dried (Na2SO4), filtered and concentrated. The crude product was purified by flash chromatography EtOAc/Hex (0-100%) to give methyl 4-(8-bromo-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamido)-3-chlorobenzoate (yield 65%). MS: (ESI+) 508.2

Workup

  1. stirringThe reaction mixture was stirred for 16 hr
  2. customThe reaction mixture was quenched with sat. NH4Cl
  3. extractionextracted with DCM (2×)
  4. dry with materialThe combined organics were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by flash chromatography EtOAc/Hex (0-100%)

Sources & evidence

ORD record
ord-fb03adb49a2542ef8c40426213d1a7d7
Source dataset
uspto-grants-2014_09
Patent number
US08846762B2

Reaction notes

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