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

HRID 2280645Notes

Reaction equation

HRID 2280645 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][CH:7]([O:10][C:11]2[CH:16]=[C:15]([CH3:17])[C:14]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([CH2:24][O:25][C:26]4[CH:39]=[CH:38][C:29]5[C@H:30]([CH2:33][C:34]([O:36]C)=[O:35])[CH2:31][O:32][C:28]=5[CH:27]=4)[CH:19]=3)=[C:13]([CH3:40])[CH:12]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[OH-].[Li+]>O1CCCC1.CO>[C:1]([N:4]1[CH2:5][CH2:6][CH:7]([O:10][C:11]2[CH:16]=[C:15]([CH3:17])[C:14]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([CH2:24][O:25][C:26]4[CH:39]=[CH:38][C:29]5[C@H:30]([CH2:33][C:34]([OH:36])=[O:35])[CH2:31][O:32][C:28]=5[CH:27]=4)[CH:19]=3)=[C:13]([CH3:40])[CH:12]=2)[CH2:8][CH2:9]1)(=[O:3])[CH3:2]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 89701743(S)-methyl 2-(6-((4'-((1-acetylpiperidin-4-yl)oxy)-2',6'-dimethylbiphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate

Product 1

HCID 71656908(S)-2-(6-((4'-((1-acetylpiperidin-4-yl)oxy)-2',6'-dimethylbiphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetic acidYield 84.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

(S)-Methyl 2-(6-((4′-((1-acetylpiperidin-4-yl)oxy)-2′,6′-dimethylbiphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate 6a (10 mg, 0.02 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 (0.2 mL, 0.20 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 (S)-2-(6-((4′-((1-acetylpiperidin-4-yl)oxy)-2′,6′-dimethylbiphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetic acid 6 (8 mg, yield 84.2%) 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-d07f813e573f46098dd80bca147b5048
Source dataset
uspto-grants-2015_09
Patent number
US09139548B2

Reaction notes

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