Hydrochloric Acid → (S)-2-(6-((2',6'-dimethyl-4'-((1-propionylazetidin-3-yl)oxy)biphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetic acid

HRID 2280663Notes

Reaction equation

HRID 2280663 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([O:8][CH:9]2[CH2:12][N:11]([C:13](=[O:16])[CH2:14][CH3:15])[CH2:10]2)[CH:5]=[C:4]([CH3:17])[C:3]=1[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([CH2:24][O:25][C:26]2[CH:39]=[CH:38][C:29]3[C@H:30]([CH2:33][C:34]([O:36]C)=[O:35])[CH2:31][O:32][C:28]=3[CH:27]=2)[CH:19]=1.[OH-].[Li+].Cl.O>CO>[CH3:1][C:2]1[CH:7]=[C:6]([O:8][CH:9]2[CH2:12][N:11]([C:13](=[O:16])[CH2:14][CH3:15])[CH2:10]2)[CH:5]=[C:4]([CH3:17])[C:3]=1[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([CH2:24][O:25][C:26]2[CH:39]=[CH:38][C:29]3[C@H:30]([CH2:33][C:34]([OH:36])=[O:35])[CH2:31][O:32][C:28]=3[CH:27]=2)[CH:19]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 3939Lithium HydroxideHCID 117699335(S)-methyl 2-(6-((2',6'-dimethyl-4'-((1-propionylazetidin-3-yl)oxy)biphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate

Product 1

HCID 71657092(S)-2-(6-((2',6'-dimethyl-4'-((1-propionylazetidin-3-yl)oxy)biphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetic acidYield 43.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The crude (S)-methyl 2-(6-((2′,6′-dimethyl-4′-((1-propionylazetidin-3-yl)oxy)biphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate 14d (45 mg, 0.09 mmol) was dissolved in 3 mL of methanol, followed by addition of 1M aqueous lithium hydroxide solution (0.5 mL, 0.50 mmol). The reaction solution was stirred for 3 hours. To the resulting solution, 1M hydrochloric acid was added dropwise to adjust the pH to 3, 3 mL of water were added, and then the solution was concentrated under reduced pressure 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-((2′,6′-dimethyl-4′-((1-propionylazetidin-3-yl)oxy)biphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetic acid 14 (20 mg, yield 43.0%) as a yellow solid.

Workup

  1. additionwere added
  2. concentrationthe solution was concentrated under reduced pressure
  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-619b4ae184cf438e8f86f3911ba087a1
Source dataset
uspto-grants-2015_09
Patent number
US09139548B2

Reaction notes

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