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

HRID 2280678Notes

Reaction equation

HRID 2280678 reaction equation
[F:1][C:2]1[C:3]([CH3:37])=[C:4]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([CH2:21][O:22][C:23]3[CH:36]=[CH:35][C:26]4[C@H:27]([CH2:30][C:31]([O:33]C)=[O:32])[CH2:28][O:29][C:25]=4[CH:24]=3)[CH:16]=2)[C:5]([CH3:14])=[CH:6][C:7]=1[O:8][C@H:9]1[CH2:13][CH2:12][O:11][CH2:10]1.[OH-].[Li+]>CO.O1CCCC1>[F:1][C:2]1[C:3]([CH3:37])=[C:4]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([CH2:21][O:22][C:23]3[CH:36]=[CH:35][C:26]4[C@H:27]([CH2:30][C:31]([OH:33])=[O:32])[CH2:28][O:29][C:25]=4[CH:24]=3)[CH:16]=2)[C:5]([CH3:14])=[CH:6][C:7]=1[O:8][C@H:9]1[CH2:13][CH2:12][O:11][CH2:10]1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 89701792methyl 2-((S)-6-((3'-fluoro-2',6'-dimethyl-4'-(((S)-tetrahydrofuran-3-yl)oxy)biphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate

Product 1

HCID 716570962-((S)-6-((3'-fluoro-2',6'-dimethyl-4'-(((S)-tetrahydrofuran-3-yl)oxy)biphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetic acidYield 57.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Methyl 2-((S)-6-((3′-fluoro-2′,6′-dimethyl-4′-(((S)-tetrahydrofuran-3-yl)oxy) biphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate 19d (150 mg, 0.30 mmol) was dissolved in 4 mL of a mixture of the solvents of methanol and tetrahydrofuran (V/V=1:1), followed by addition of 1M aqueous lithium hydroxide solution (1.5 mL, 1.50 mmol). The reaction solution was stirred for 2 hours. The resulting solution was concentrated under reduced pressure, mixed with 10 mL of water, 1M 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-((3′-fluoro-2′,6′-dimethyl-4′-(((S)-tetrahydrofuran-3-yl)oxy)biphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetic acid 19 (85 mg, yield 57.8%) as a white solid.

Workup

  1. concentrationThe resulting solution was concentrated under reduced pressure
  2. additionmixed 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-dcc3b1c01a1b4fd8a0a300a5a1e34059
Source dataset
uspto-grants-2015_09
Patent number
US09139548B2

Reaction notes

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