Lithium hydroxide, monohydrate → N-(2,2-Diphenylethyl)-N-(2-chloro-3-trifluoromethylbenzyl)-3-(3-carboxyphenoxy)propylamine, hydrochloride

HRID 229116Notes

Reaction equation

HRID 229116 reaction equation
C[O:2][C:3](=[O:41])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([O:10][CH2:11][CH2:12][CH2:13][N:14]([CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([F:39])([F:38])[F:37])[C:31]=2[Cl:40])[CH2:15][CH:16]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:5]=1.O[Li].O>C1COCC1.O>[ClH:40].[Cl:40][C:31]1[C:32]([C:36]([F:37])([F:38])[F:39])=[CH:33][CH:34]=[CH:35][C:30]=1[CH2:29][N:14]([CH2:15][CH:16]([C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH2:13][CH2:12][CH2:11][O:10][C:6]1[CH:5]=[C:4]([CH:9]=[CH:8][CH:7]=1)[C:3]([OH:41])=[O:2]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrate2×HCID 577571333-{3-[(2-Chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}-benzoic acid methyl ester

Product 1

HCID 68861721N-(2,2-Diphenylethyl)-N-(2-chloro-3-trifluoromethylbenzyl)-3-(3-carboxyphenoxy)propylamine, hydrochlorideYield 134.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}-benzoic acid methyl ester (0.200 g, 0.344 mmol) in THF (7.5 mL) and H2O (2.5 mL) at RT LiOH.H2O (0.029 g, 0.688 mmol) was added. The mixture was stirred overnight at RT. The mixture was then treated with more LiOH.H2O (0.058 g, 1.376 mmol) and heated at 50° C. overnight. The completed reaction was cooled to 0° C. and was quenched with a minimal amount of H2O. The mixture was the acidified to a pH=2 with concentrated HCl. The mixture was then extracted three times with EtOAc and was dried, filtered and concentrated to afford a foam that was purified via preparative HPLC (TMC CombiPrep PDS, 75×30 mm, 25 mL/min, acetonitrile:H2O, UV detection at 254 nm) to yield the title compound (0.14 g, 72%); MS (ES+) m/e 569 [M+H]+.

Workup

  1. temperatureheated at 50° C. overnight
  2. customThe completed reaction
  3. temperaturewas cooled to 0° C.
  4. customwas quenched with a minimal amount of H2O
  5. extractionThe mixture was then extracted three times with EtOAc
  6. customwas dried
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto afford a foam that
  10. customwas purified via preparative HPLC (TMC CombiPrep PDS, 75×30 mm, 25 mL/min, acetonitrile:H2O, UV detection at 254 nm)

Sources & evidence

ORD record
ord-fb01fd29e94d429683011d265cff3a60
Source dataset
uspto-grants-2009_07
Patent number
US07560586B2

Reaction notes

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