Potassium Carbonate → (1R)-8-Chloro-2,3,4,5-tetrahydro-1-methyl-1H-3-benzazepine hydrochloride hemihydrate
Reaction equation
C(=O)([O-])[O-:2].[K+].[K+].[OH-].[Na+].C(C(C(C([O-])=O)O)O)([O-])=O.[Cl:19][C:20]1[CH:21]=[CH:22][C:23]2[CH2:29][CH2:28][NH2+:27][CH2:26][C@H:25]([CH3:30])[C:24]=2[CH:31]=1.[Cl:32][C:33]1[CH:34]=[CH:35][C:36]2[CH2:42][CH2:41][NH2+:40][CH2:39][C@H:38]([CH3:43])[C:37]=2[CH:44]=1>>[OH2:2].[ClH:19].[Cl:32][C:33]1[CH:34]=[CH:35][C:36]2[CH2:42][CH2:41][NH:40][CH2:39][C@H:38]([CH3:43])[C:37]=2[CH:44]=1.[Cl:19][C:20]1[CH:21]=[CH:22][C:23]2[CH2:29][CH2:28][NH:27][CH2:26][C@H:25]([CH3:30])[C:24]=2[CH:31]=1.[ClH:19]Participants
Procedure
One base that is particularly useful in neutralizing the hemitartrate salt is aqueous potassium carbonate. In contrast, it was found that when aqueous NaOH was used to neutralize (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-benzo[d]azepinium hemitartrate a difficult-to-separate emulsion was generated. However, aqueous potassium carbonate can be used that is essentially free of any emulsion when extracting the free base (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine after neutralizing. In addition, it was also found that ethyl acetate was particularly suitable for use in the steps of neutralizing, contacting and crystallizing to provide (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride hemihydrate. Ethyl acetate was also found particularly useful for the dissolution of concentrations of water appropriate for crystallizing the (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride hemihydrate.
Workup
- extractionextracting the free base (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine
- customcrystallizing
Sources & evidence
- ORD record
- ord-385e5cd2840d490d8a524a025f706831
- Source dataset
- uspto-grants-2014_08
- Patent number
- US08802845B2
Reaction notes
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