Hydrochloric Acid → [4-(3-{3-[(2-Chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-piperazin-1-yl]-acetic acid hydrochloride salt

HRID 902703Notes

Reaction equation

HRID 902703 reaction equation
C[O:2][C:3](=[O:48])[CH2:4][N:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:18][CH2:19][CH2:20][N:21]([CH2:36][C:37]3[CH:42]=[CH:41][CH:40]=[C:39]([C:43]([F:46])([F:45])[F:44])[C:38]=3[Cl:47])[CH2:22][CH:23]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH:12]=2)[CH2:7][CH2:6]1.O.[OH-].[Li+].Cl>C1COCC1.O>[ClH:47].[Cl:47][C:38]1[C:39]([C:43]([F:45])([F:44])[F:46])=[CH:40][CH:41]=[CH:42][C:37]=1[CH2:36][N:21]([CH2:22][CH:23]([C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH2:20][CH2:19][CH2:18][O:17][C:13]1[CH:12]=[C:11]([N:8]2[CH2:7][CH2:6][N:5]([CH2:4][C:3]([OH:48])=[O:2])[CH2:10][CH2:9]2)[CH:16]=[CH:15][CH:14]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 69252741[4-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-piperazin-1-yl]-acetic Acid Methyl Ester

Product 1

HCID 69254920[4-(3-{3-[(2-Chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-piperazin-1-yl]-acetic acid hydrochloride saltYield 169.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirring solution of [4-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-piperazin-1-yl]-acetic acid methyl ester (99 mg, 0.146 mmol) in a mixture of THF and water (3:1; 12 ml) was added lithium hydroxide monohydrate (8 mg, 0.192 mmol). The resulting mixture was stirred at room temperature for 18 hours and then acidified with 1 M aqueous HCl (0.2 ml). The mixture was concentrated in vacuo, water (5 mL) was added, and the crude material was extracted with EtOAc (3×). The combined organic layers were washed with brine (1×), dried over sodium sulfate, and filtered. The organic layer was concentrated, and the crude amine was treated with 1 M HCl (Et2O). The resulting precipitate was dried under vacuum to afford the title compound as a solid (87 mg, 97%). MS(ES) m/e 666.0 (M+).

Workup

  1. concentrationThe mixture was concentrated in vacuo, water (5 mL)
  2. additionwas added
  3. extractionthe crude material was extracted with EtOAc (3×)
  4. washThe combined organic layers were washed with brine (1×)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationThe organic layer was concentrated
  8. additionthe crude amine was treated with 1 M HCl (Et2O)
  9. customThe resulting precipitate was dried under vacuum

Sources & evidence

ORD record
ord-dfdc3195aaf14f58acb31259dbbaf25f
Source dataset
uspto-grants-2008_04
Patent number
US07365085B2

Reaction notes

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