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

HRID 2280647Notes

Reaction equation

HRID 2280647 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-].[Li+]>O1CCCC1.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 2

HCID 3939Lithium HydroxideHCID 89701802methyl 2-((S)-6-((2',6'-dimethyl-4'-(((S)-1-(methylsulfonyl)pyrrolidin-3-yl)oxy)biphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate

Product 1

HCID 716569102-((S)-6-((2',6'-dimethyl-4'-(((S)-1-(methylsulfonyl)pyrrolidin-3-yl)oxy)biphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetic acidYield 101.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Methyl 2-((S)-6-((2′,6′-dimethyl-4′-(((S)-1-(methylsulfonyl)pyrrolidin-3-yl)oxy)biphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate 8b (30 mg, 0.05 mmol) was dissolved in 2 mL of a mixture of the solvents tetrahydrofuran and methanol (V/V=1:1), followed by addition of 1M aqueous lithium hydroxide solution (0.1 mL, 0.10 mmol). The reaction solution was stirred for 2 hours. The resulting solution was concentrated under reduced pressure, 1M hydrochloric acid was added dropwise to adjust the pH to 5 and extracted 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 to obtain the title compound 2-((S)-6-((2′,6′-dimethyl-4′-(((S)-1-(methylsulfonyl)pyrrolidin-3-yl)oxy)biphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetic acid 8 (28 mg, yield 94.2%) as a white solid.

Workup

  1. concentrationThe resulting solution was concentrated under reduced pressure, 1M hydrochloric acid
  2. additionwas added dropwise
  3. extractionextracted with ethyl acetate (20 mL×2)
  4. washThe combined organic extracts were washed with saturated sodium chloride solution (30 mL)
  5. dry with materialdried with anhydrous magnesium sulphate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-5d1e83ac022041b7ae66e80b5aae23d8
Source dataset
uspto-grants-2015_09
Patent number
US09139548B2

Reaction notes

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