Lithium hydroxide, monohydrate → 5-{[2-(4-Carboxyphenyl)ethyl][2-(2-{[4-(5-chloro-1,3-benzoxazol-2-yl)benzyl]oxy}phenyl)ethyl]-amino}-5,6,7,8-tetrahydroquinoline-2-carboxylic acid

HRID 875356Notes

Reaction equation

HRID 875356 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([C:10]3[CH:53]=[CH:52][C:13]([CH2:14][O:15][C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=4[CH2:22][CH2:23][N:24]([CH2:40][CH2:41][C:42]4[CH:47]=[CH:46][C:45]([C:48]([O:50]C)=[O:49])=[CH:44][CH:43]=4)[CH:25]4[CH2:34][CH2:33][CH2:32][C:31]5[N:30]=[C:29]([C:35]([O:37]CC)=[O:36])[CH:28]=[CH:27][C:26]4=5)=[CH:12][CH:11]=3)=[N:7][C:6]=2[CH:54]=1.O.[OH-].[Li+]>C1COCC1.O>[C:48]([C:45]1[CH:46]=[CH:47][C:42]([CH2:41][CH2:40][N:24]([CH2:23][CH2:22][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[O:15][CH2:14][C:13]2[CH:12]=[CH:11][C:10]([C:8]3[O:9][C:5]4[CH:4]=[CH:3][C:2]([Cl:1])=[CH:54][C:6]=4[N:7]=3)=[CH:53][CH:52]=2)[CH:25]2[CH2:34][CH2:33][CH2:32][C:31]3[N:30]=[C:29]([C:35]([OH:37])=[O:36])[CH:28]=[CH:27][C:26]2=3)=[CH:43][CH:44]=1)([OH:50])=[O:49]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 86709810Ethyl 5-([2-(2-{[4-(5-chloro-1,3-benzoxazol-2-yl)benzyl]oxy}phenyl)ethyl]{2-[4-(methoxy-carbonyl)phenyl]ethyl}amino)-5,6,7,8-tetrahydroquinoline-2-carboxylate

Product 1

HCID 730577385-{[2-(4-Carboxyphenyl)ethyl][2-(2-{[4-(5-chloro-1,3-benzoxazol-2-yl)benzyl]oxy}phenyl)ethyl]-amino}-5,6,7,8-tetrahydroquinoline-2-carboxylic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

45 mg (0.06 mmol) of ethyl 5-([2-(2-{[4-(5-chloro-1,3-benzoxazol-2-yl)benzyl]oxy}-phenyl)ethyl]-{2-[4-(methoxycarbonyl)phenyl]ethyl}amino)-5,6,7,8-tetrahydroquinoline-2-carboxylate (Enantiomer 2, Example 64A) were taken up in 4 ml of THF and 2 ml of water, and 8 mg (0.18 mmol) of lithium hydroxide monohydrate were added. The reaction was stirred at 60° C. overnight. After the reaction had gone to completion, the THF was removed on a rotary evaporator and the mixture that remained was diluted with water. The mixture was then acidified to pH 4-5 using acetic acid and extracted repeatedly with ethyl acetate. The combined organic phases were dried over magnesium sulphate, filtered and concentrated to dryness. This gave 13 mg (0.02 mmol, 32% of theory) of the title compound.

Workup

  1. customthe THF was removed on a rotary evaporator
  2. additionthe mixture that remained was diluted with water
  3. extractionextracted repeatedly with ethyl acetate
  4. dry with materialThe combined organic phases were dried over magnesium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-c9496bb94f6a4cc5b28f1e44e7cbf4dc
Source dataset
uspto-grants-2015_03
Patent number
US08981104B2

Reaction notes

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