Hydrochloric Acid → (2-Chloro-3-trifluoromethyl-benzyl)-(2,2-diphenyl-ethyl)-{3-[3-(2-methylamino-ethyl)-phenoxy]-propyl}-amine hydrochloride salt

HRID 902693Notes

Reaction equation

HRID 902693 reaction equation
[Cl:1][C:2]1[C:38]([C:39]([F:42])([F:41])[F:40])=[CH:37][CH:36]=[CH:35][C:3]=1[CH2:4][N:5]([CH2:21][CH:22]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH2:6][CH2:7][CH2:8][O:9][C:10]1[CH:11]=[C:12]([CH2:16][C:17]([NH:19][CH3:20])=O)[CH:13]=[CH:14][CH:15]=1.Cl>C1COCC1>[ClH:1].[Cl:1][C:2]1[C:38]([C:39]([F:40])([F:41])[F:42])=[CH:37][CH:36]=[CH:35][C:3]=1[CH2:4][N:5]([CH2:21][CH:22]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)[CH2:6][CH2:7][CH2:8][O:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([CH2:16][CH2:17][NH:19][CH3:20])[CH:11]=1

Participants

4

Reactant 2

HCID 313Hydrochloric Acid2×HCID 117646132-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-N-methyl-acetamide2×

Product 1

HCID 69253092(2-Chloro-3-trifluoromethyl-benzyl)-(2,2-diphenyl-ethyl)-{3-[3-(2-methylamino-ethyl)-phenoxy]-propyl}-amine hydrochloride saltYield 99.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirring solution of 2-(3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-N-methyl-acetamide (101 mg, 0.17 mmol) (Intermediate 3 above) in anhydrous THF (10 mL) was added BH3 THF (0.34 ml, 1 M solution in THF). The resulting solution was then heated to reflux for 1.5 hours. Aqeous HCl (0.34 ml. 6 M) was then added to the reaction and the mixture was heated at reflux for 30 min. After cooling to RT, the reaction mixture was concentrated in vacuo and extracted with EtOAc (3×). The combined organic layers were washed with brine (1×), dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography over silica gel (silica gel 60, EM science) using 5% MeOH:dichloro-methane as eluent. The free base was dissolved in dichloromethane, 1 eq. of HCl (1M in Et2O) was added, and the mixture was evaporated to afford the title compound as a white solid (52 mg, 50%). MS(ES) m/e 581.4 (M+).

Workup

  1. temperatureThe resulting solution was then heated
  2. temperatureto reflux for 1.5 hours
  3. temperaturethe mixture was heated
  4. temperatureat reflux for 30 min
  5. concentrationthe reaction mixture was concentrated in vacuo
  6. extractionextracted with EtOAc (3×)
  7. washThe combined organic layers were washed with brine (1×)
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude product was purified by column chromatography over silica gel (silica gel 60, EM science)
  12. dissolutionThe free base was dissolved in dichloromethane
  13. customthe mixture was evaporated

Sources & evidence

ORD record
ord-dae9fb5583e441ceb973b483352627a8
Source dataset
uspto-grants-2008_04
Patent number
US07365085B2

Reaction notes

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