Hydrochloric Acid → Tolvaptan

HRID 1886975Notes

Reaction equation

HRID 1886975 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-ed4c71dcc6bf47b1a3771b47405242a9
Source dataset
uspto-grants-2013_08
Patent number
US08501730B2

Reaction notes

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