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

HRID 2280654Notes

Reaction equation

HRID 2280654 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([O:8][C@@H:9]2[CH2:13][CH2:12][N:11]([S:14]([CH3:17])(=[O:16])=[O:15])[CH2:10]2)[CH:5]=[C:4]([CH3:18])[C:3]=1[C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([CH2:25][O:26][C:27]2[CH:40]=[CH:39][C:30]3[C@H:31]([CH2:34][C:35]([O:37]C)=[O:36])[CH2:32][O:33][C:29]=3[CH:28]=2)[CH:20]=1.[OH-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CO>[CH3:18][C:4]1[CH:5]=[C:6]([O:8][C@@H:9]2[CH2:13][CH2:12][N:11]([S:14]([CH3:17])(=[O:16])=[O:15])[CH2:10]2)[CH:7]=[C:2]([CH3:1])[C:3]=1[C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([CH2:25][O:26][C:27]2[CH:40]=[CH:39][C:30]3[C@H:31]([CH2:34][C:35]([OH:37])=[O:36])[CH2:32][O:33][C:29]=3[CH:28]=2)[CH:20]=1

Participants

5

Reactant 3

HCID 311Citric AcidHCID 14798Sodium HydroxideHCID 117699363methyl 2-((S)-6-((2',6'-dimethyl-4'-(((R)-1-(methylsulfonyl)pyrrolidin-3-yl)oxy)biphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate

Product 1

HCID 716570002-((S)-6-((2',6'-dimethyl-4'-(((R)-1-(methylsulfonyl)pyrrolidin-3-yl)oxy)biphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetic acidYield 100%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Methyl 2-((S)-6-((2′,6′-dimethyl-4′-(((R)-1-(methylsulfonyl)pyrrolidin-3-yl)oxy)biphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate 11d (71 mg, 0.13 mmol) was dissolved in 10 mL of methanol, followed by addition of 2M aqueous sodium hydroxide solution (0.5 mL, 1 mmol). The reaction solution was stirred for 2 hours. To the resulting solution, 1M citric acid was added dropwise to adjust the pH to 4˜5. The organic phase was dried with anhydrous magnesium sulphate and filtered. The filtrate was concentrated under reduced pressure to obtain the title compound 2-((S)-6-((2′,6′-dimethyl-4′-(((R)-1-(methylsulfonyl)pyrrolidin-3-yl)oxy)biphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetic acid 11 (70 mg, yield 100%) as a yellow solid.

Workup

  1. dry with materialThe organic phase was dried with anhydrous magnesium sulphate
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-d835072f78af4835b9c250ab83f98bed
Source dataset
uspto-grants-2015_09
Patent number
US09139548B2

Reaction notes

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