Lithium Hydroxide → 2-((S)-6-((4'-(((S)-1-acetylpyrrolidin-3-yl)oxy)-2',6'-dimethylbiphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetic acid

HRID 2280649Notes

Reaction equation

HRID 2280649 reaction equation
[C:1]([N:4]1[CH2:8][CH2:7][C@H:6]([O:9][C:10]2[CH:15]=[C:14]([CH3:16])[C:13]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([CH2:23][O:24][C:25]4[CH:38]=[CH:37][C:28]5[C@H:29]([CH2:32][C:33]([O:35]C)=[O:34])[CH2:30][O:31][C:27]=5[CH:26]=4)[CH:18]=3)=[C:12]([CH3:39])[CH:11]=2)[CH2:5]1)(=[O:3])[CH3:2].[OH-].[Li+]>O1CCCC1.CO>[C:1]([N:4]1[CH2:8][CH2:7][C@H:6]([O:9][C:10]2[CH:11]=[C:12]([CH3:39])[C:13]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([CH2:23][O:24][C:25]4[CH:38]=[CH:37][C:28]5[C@H:29]([CH2:32][C:33]([OH:35])=[O:34])[CH2:30][O:31][C:27]=5[CH:26]=4)[CH:18]=3)=[C:14]([CH3:16])[CH:15]=2)[CH2:5]1)(=[O:3])[CH3:2]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 89701735methyl 2-((S)-6-((4'-(((S)-1-acetylpyrrolidin-3-yl)oxy)-2',6'-dimethylbiphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate

Product 1

HCID 716569982-((S)-6-((4'-(((S)-1-acetylpyrrolidin-3-yl)oxy)-2',6'-dimethylbiphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetic acidYield 51.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

The crude methyl 2-((S)-6-((4′-(((S)-1-acetylpyrrolidin-3-yl)oxy)-2′,6′-dimethylbiphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate 9a (40 mg, 0.08 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 (0.4 mL, 0.40 mmol). The reaction solution was stirred for 3 hours. The resulting solution was concentrated under reduced pressure. The residue was mixed with 10 mL of water, 1M hydrochloric acid was added dropwise to adjust the pH to 3, 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 and the residue was purified by TLC with elution system A to obtain the title compound 2-((S)-6-((4′-(((S)-1-acetylpyrrolidin-3-yl)oxy)-2′,6′-dimethylbiphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetic acid 9 (20 mg, yield 51.3%) as a white solid.

Workup

  1. concentrationThe resulting solution was concentrated under reduced pressure
  2. additionThe residue was mixed with 10 mL of water, 1M hydrochloric acid
  3. additionwas added dropwise
  4. extractionextracted with ethyl acetate (20 mL×2)
  5. washThe combined organic extracts were washed with saturated sodium chloride solution (30 mL)
  6. dry with materialdried with anhydrous magnesium sulphate
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customthe residue was purified by TLC with elution system

Sources & evidence

ORD record
ord-c473fafdb5224e2287fea8e7d87953c4
Source dataset
uspto-grants-2015_09
Patent number
US09139548B2

Reaction notes

Loading…