Hydrochloric Acid → (S)-2-(6-((2',6'-dimethyl-4'-((1-(methylsulfonyl)piperidin-4-yl)oxy)biphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetic acid

HRID 2280643Notes

Reaction equation

HRID 2280643 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([O:8][CH:9]2[CH2:14][CH2:13][N:12]([S:15]([CH3:18])(=[O:17])=[O:16])[CH2:11][CH2:10]2)[CH:5]=[C:4]([CH3:19])[C:3]=1[C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([CH2:26][O:27][C:28]2[CH:41]=[CH:40][C:31]3[C@H:32]([CH2:35][C:36]([O:38]C)=[O:37])[CH2:33][O:34][C:30]=3[CH:29]=2)[CH:21]=1.[OH-].[Na+].Cl>C(O)C>[CH3:19][C:4]1[CH:5]=[C:6]([O:8][CH:9]2[CH2:14][CH2:13][N:12]([S:15]([CH3:18])(=[O:17])=[O:16])[CH2:11][CH2:10]2)[CH:7]=[C:2]([CH3:1])[C:3]=1[C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([CH2:26][O:27][C:28]2[CH:41]=[CH:40][C:31]3[C@H:32]([CH2:35][C:36]([OH:38])=[O:37])[CH2:33][O:34][C:30]=3[CH:29]=2)[CH:21]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 89701796(S)-methyl 2-(6-((2',6'-dimethyl-4'-((1-(methylsulfonyl)piperidin-4-yl)oxy)biphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate

Product 1

HCID 71656907(S)-2-(6-((2',6'-dimethyl-4'-((1-(methylsulfonyl)piperidin-4-yl)oxy)biphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetic acidYield 44%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

The crude (S)-methyl 2-(6-((2′,6′-dimethyl-4′-((1-(methylsulfonyl)piperidin-4-yl)oxy)biphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate 5a (28 mg, 0.05 mmol) was dissolved in 5 mL of ethanol, followed by addition of 1M aqueous sodium hydroxide solution (0.5 mL, 0.50 mmol). The reaction solution was reacted for 1 hour. 1M hydrochloric acid was added dropwise to the resulting solution to adjust the pH to 5, followed by extraction with ethyl acetate (20 mL×2). The combined organic extracts were washed with saturated sodium chloride solution (30 mL), dried with anhydrous magnesium sulphate, and filtered. The filtrate was concentrated under reduced pressure and the residue was purified using a method of preparative separation to obtain the title compound (S)-2-(6-((2′,6′-dimethyl-4′-((1-(methylsulfonyl)piperidin-4-yl)oxy)biphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetic acid 5 (12 mg, yield 44.0%) as a white solid.

Workup

  1. customThe reaction solution was reacted for 1 hour
  2. extractionfollowed by extraction with ethyl acetate (20 mL×2)
  3. washThe combined organic extracts were washed with saturated sodium chloride solution (30 mL)
  4. dry with materialdried with anhydrous magnesium sulphate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe residue was purified
  8. customa method of preparative separation

Sources & evidence

ORD record
ord-94aab665bfcc4d5ba800fb491ab0114b
Source dataset
uspto-grants-2015_09
Patent number
US09139548B2

Reaction notes

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