Hydrochloric Acid → Tolvaptan

HRID 2389240Notes

Reaction equation

HRID 2389240 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([C:12](=[O:30])[C:13]3[CH:18]=[CH:17][C:16]([NH:19][C:20](=[O:28])[C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[CH3:27])=[CH:15][C:14]=3[CH3:29])[CH2:10][CH2:9][CH2:8][C:7](=[O:31])[C:6]=2[CH:32]=1.[BH4-].[Na+].Cl>CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([C:12](=[O:30])[C:13]3[CH:18]=[CH:17][C:16]([NH:19][C:20](=[O:28])[C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[CH3:27])=[CH:15][C:14]=3[CH3:29])[CH2:10][CH2:9][CH2:8][CH:7]([OH:31])[C:6]=2[CH:32]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 113628435-Dehydro Tolvaptan

Product 1

HCID 216237TolvaptanYield 92.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

7-Chloro-1-[2-methyl-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1-benzazepin-5-one (3.2 g, 7.1 mM) is suspended in methanol (27 mL), and thereto is added at one time crystalline sodium borohydride (96 mg=2.5 mM), and the mixture is reacted for about one hours. To the reaction mixture is added dropwise 0.5% diluted hydrochloric acid (9.3 mL), and the mixture is stirred at room temperature and then cooled. The precipitated crystals are separated by filtration, and dried at room temperature to give the desired 7-chloro-5-hydroxy-1-[2-methyl-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1-benzazepine (2.97 g) as white powder (Yield 92%, Mp 224.5-225.5° C.).

Workup

  1. customthe mixture is reacted for about one hours
  2. temperaturecooled
  3. customThe precipitated crystals are separated by filtration
  4. customdried at room temperature

Sources & evidence

ORD record
ord-f36bc83d46b648bf81ea28c9aff2ced5
Source dataset
uspto-grants-2012_09
Patent number
US08273735B2

Reaction notes

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