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

HRID 2280674Notes

Reaction equation

HRID 2280674 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([CH3:14])=[CH:12][C:11]([O:15][C@H:16]3[CH2:20][CH2:19][O:18][CH2:17]3)=[CH:10][C:9]=2[CH3:21])=[CH:4][C:3]=1[CH2:22][O:23][C:24]1[CH:37]=[CH:36][C:27]2[C@H:28]([CH2:31][C:32]([O:34]C)=[O:33])[CH2:29][O:30][C:26]=2[CH:25]=1.[OH-].[Li+]>O1CCCC1.CO.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([CH3:21])=[CH:10][C:11]([O:15][C@H:16]3[CH2:20][CH2:19][O:18][CH2:17]3)=[CH:12][C:13]=2[CH3:14])=[CH:4][C:3]=1[CH2:22][O:23][C:24]1[CH:37]=[CH:36][C:27]2[C@H:28]([CH2:31][C:32]([OH:34])=[O:33])[CH2:29][O:30][C:26]=2[CH:25]=1

Participants

6

Reactant 2

HCID 3939Lithium HydroxideHCID 89701770methyl 2-((S)-6-((4-fluoro-2',6'-dimethyl-4'-(((S)-tetrahydrofuran-3-yl)oxy)biphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate

Product 1

HCID 716210062-((S)-6-((4-fluoro-2',6'-dimethyl-4'-(((S)-tetrahydrofuran-3-yl)oxy)biphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetic acidYield 67.7%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Methyl 2-((S)-6-((4-fluoro-2′,6′-dimethyl-4′-(((S)-tetrahydrofuran-3-yl)oxy) biphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate 18e (150 mg, 0.30 mmol) was dissolved in 4.5 mL of a mixture of the solvents tetrahydrofuran, methanol and water (V/V=1:3:0.5), followed by addition of 1M aqueous lithium hydroxide solution (1 mL, 1 mmol). The reaction solution was stirred for 12 hours. The resulting solution was concentrated under reduced pressure. The residue was mixed with 10 mL of water, 2M hydrochloric acid was added dropwise to adjust the pH to 2˜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-fluoro-2′,6′-dimethyl-4′-(((S)-tetrahydrofuran-3-yl)oxy)biphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetic acid 18 (100 mg, yield 66.7%) as a white solid.

Workup

  1. concentrationThe resulting solution was concentrated under reduced pressure
  2. additionThe residue was mixed with 10 mL of water, 2M 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-23942f85cfb5454a9df4234c45eb0bda
Source dataset
uspto-grants-2015_09
Patent number
US09139548B2

Reaction notes

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