Tetrahydrofuran → 5-ethoxy-carbonylmethylidene-7-chloro-1-[2-methyl-4-(2-methylbenzoyl-amino)benzoyl]-2,3,4,5-tetrahydro-1H-benzoazepine

HRID 54749Notes

Reaction equation

HRID 54749 reaction equation
[H-].[Na+].[CH2:3]([O:5]P(CC(OCC)=O)(OCC)=O)[CH3:4].[O:17]=[C:18]1[C:24]2[CH:25]=[C:26]([Cl:29])[CH:27]=[CH:28][C:23]=2[N:22]([C:30](=[O:48])[C:31]2[CH:36]=[CH:35][C:34]([NH:37][C:38](=[O:46])[C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=3[CH3:45])=[CH:33][C:32]=2[CH3:47])[CH2:21][CH2:20][CH2:19]1.O1CC[CH2:51][CH2:50]1>>[CH2:50]([O:17][CH:18]1[C:24]2[CH:25]=[C:26]([Cl:29])[CH:27]=[CH:28][C:23]=2[N:22]([C:30](=[O:48])[C:31]2[CH:36]=[CH:35][C:34]([NH:37][C:38](=[O:46])[C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=3[CH3:45])=[CH:33][C:32]=2[CH3:47])[C:21](=[C:4]=[C:3]=[O:5])[CH2:20][CH2:19]1)[CH3:51]

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 13345Triethyl phosphonoacetateHCID 24758Sodium hydrideHCID 113628435-Dehydro Tolvaptan

Product 1

HCID 867507475-ethoxy-carbonylmethylidene-7-chloro-1-[2-methyl-4-(2-methylbenzoyl-amino)benzoyl]-2,3,4,5-tetrahydro-1H-benzoazepine

Procedure

0.85 g of 60% sodium hydride was added to 200 ml of tetrahydrofuran. Thereto was dropwise added 4.68 ml of ethyl diethylphosphonoacetate with ice-cooling and stirring. The mixture was stirred for 10 minutes with ice-cooling. To the reaction mixture was added 2.10 g of 5-oxo-7-chloro-1-[2-methyl-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetra-hydro-1H-benzoazepine. The mixture was stirred at room temperature for 6 hours. The reaction mixture was poured into 200 ml of ice water. The resulting mixture was subjected to extraction with 300 ml of ethyl acetate. The extract was washed with 300 ml of an aqueous sodium chloride solution, then dried over magnesium sulfate, and subjected to distillation to remove the solvent. The residue was purified by silica gel column chromatography (elutant: ethyl acetate/n-hexane=1/2) to obtain 2.22 g of 5-ethoxy-carbonylmethylidene-7-chloro-1-[2-methyl-4-(2-methylbenzoyl-amino)benzoyl]-2,3,4,5-tetrahydro-1H-benzoazepine as a mixture of the E form and the Z form.

Workup

  1. temperaturecooling
  2. stirringThe mixture was stirred for 10 minutes with ice-
  3. temperaturecooling
  4. stirringThe mixture was stirred at room temperature for 6 hours
  5. extractionThe resulting mixture was subjected to extraction with 300 ml of ethyl acetate
  6. washThe extract was washed with 300 ml of an aqueous sodium chloride solution
  7. dry with materialdried over magnesium sulfate
  8. distillationsubjected to distillation
  9. customto remove the solvent
  10. customThe residue was purified by silica gel column chromatography (elutant: ethyl acetate/n-hexane=1/2)

Sources & evidence

ORD record
ord-822d9c0c8a424263a043c7b10e0144a7
Source dataset
uspto-grants-1997_04
Patent number
US05622947

Reaction notes

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