Sodium Hydroxide → 5-{[2-(4-Carboxyphenyl)ethyl][2-(2-{[3-chloro-4'-(trifluoromethyl)biphenyl-4-yl]methoxy}-phenyl)ethyl]amino}-5,6,7,8-tetrahydroquinoline-2-carboxylic acid

HRID 875357Notes

Reaction equation

HRID 875357 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:46]2[CH:51]=[CH:50][C:49]([C:52]([F:55])([F:54])[F:53])=[CH:48][CH:47]=2)[CH:5]=[CH:6][C:7]=1[CH2:8][O:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[CH2:16][CH2:17][N:18]([CH2:34][CH2:35][C:36]1[CH:41]=[CH:40][C:39]([C:42]([O:44]C)=[O:43])=[CH:38][CH:37]=1)[CH:19]1[CH2:28][CH2:27][CH2:26][C:25]2[N:24]=[C:23]([C:29]([O:31]CC)=[O:30])[CH:22]=[CH:21][C:20]1=2.[OH-].[Na+]>O1CCOCC1>[C:42]([C:39]1[CH:38]=[CH:37][C:36]([CH2:35][CH2:34][N:18]([CH2:17][CH2:16][C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[O:9][CH2:8][C:7]2[CH:6]=[CH:5][C:4]([C:46]3[CH:47]=[CH:48][C:49]([C:52]([F:54])([F:55])[F:53])=[CH:50][CH:51]=3)=[CH:3][C:2]=2[Cl:1])[CH:19]2[CH2:28][CH2:27][CH2:26][C:25]3[N:24]=[C:23]([C:29]([OH:31])=[O:30])[CH:22]=[CH:21][C:20]2=3)=[CH:41][CH:40]=1)([OH:44])=[O:43]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 86709816Ethyl 5-([2-(2-{[3-chloro-4'-(trifluoromethyl)biphenyl-4-yl]methoxy}phenyl)ethyl]{2-[4-(methoxycarbonyl)phenyl]ethyl}amino)-5,6,7,8-tetrahydroquinoline-2-carboxylate

Product 1

HCID 730583065-{[2-(4-Carboxyphenyl)ethyl][2-(2-{[3-chloro-4'-(trifluoromethyl)biphenyl-4-yl]methoxy}-phenyl)ethyl]amino}-5,6,7,8-tetrahydroquinoline-2-carboxylic acid

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

42 g (54.46 mmol) of ethyl 5-([2-(2-{[3-chloro-4′-(trifluoromethyl)biphenyl-4-yl]methoxy}-phenyl)ethyl]{2-[4-(methoxycarbonyl)phenyl]ethyl}amino)-5,6,7,8-tetrahydroquinoline-2-carboxylate (Enantiomer 2, Example 92A) were dissolved in 429 ml of dioxane, 163 ml of 1 N aqueous sodium hydroxide solution were added and the mixture was then stirred at room temperature overnight. After the reaction had gone to completion, the dioxane was removed on a rotary evaporator and the mixture that remained was diluted with about 750 ml of water. The mixture was then acidified to pH 4-5 using acetic acid. The precipitated solid was filtered off with suction and washed repeatedly with water (about 250 ml of water in total). The solid was then taken up in 750 ml of water and stirred at room temperature overnight. After another filtration with suction, the solid was again washed with water and then dried under high vacuum overnight using the drying agent phosphorus pentoxide. The drying agent was then removed and the solid was dried at 40° C. for a further 24 h. In this manner, 35 g (48 mmol, 88% of theory) of the title compound were obtained.

Workup

  1. customthe dioxane was removed on a rotary evaporator
  2. additionthe mixture that remained was diluted with about 750 ml of water
  3. filtrationThe precipitated solid was filtered off with suction
  4. washwashed repeatedly with water (about 250 ml of water in total)
  5. stirringstirred at room temperature overnight
  6. filtrationAfter another filtration with suction
  7. washthe solid was again washed with water
  8. customdried under high vacuum overnight
  9. customThe drying agent was then removed
  10. customthe solid was dried at 40° C. for a further 24 h

Sources & evidence

ORD record
ord-22e6d88c1e144dabaaca2c81ea72ca7d
Source dataset
uspto-grants-2015_03
Patent number
US08981104B2

Reaction notes

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