Lithium Hydroxide → (S)-2-(6-((4'-(azetidin-3-yloxy)-2',6'-dimethylbiphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetic acid

HRID 2280667Notes

Reaction equation

HRID 2280667 reaction equation
C(CC([N:6]1[CH2:9][CH:8]([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)[CH2:7]1)=O)#N.[OH-].[Li+]>O1CCCC1.CO>[NH:6]1[CH2:9][CH:8]([O:10][C:11]2[CH:12]=[C:13]([CH3:40])[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:15]([CH3:17])[CH:16]=2)[CH2:7]1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 117699401(S)-methyl 2-(6-((4'-((1-(2-cyanoacetyl)azetidin-3-yl)oxy)-2',6'-dimethylbiphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate

Product 1

HCID 71657094(S)-2-(6-((4'-(azetidin-3-yloxy)-2',6'-dimethylbiphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetic acidYield 95.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

(S)-Methyl 2-(6-((4′-((1-(2-cyanoacetyl)azetidin-3-yl)oxy)-2′,6′-dimethylbiphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate 16c (80 mg, 0.15 mmol) was dissolved in 2 mL of a mixture of the solvents of tetrahydrofuran and methanol (V/V=1:1), followed by addition of 1M aqueous lithium hydroxide solution (1 mL, 1 mmol). The reaction solution was stirred for 2 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. The residue was purified by silica gel column chromatography with elution system B to obtain the title compound (S)-2-(6-((4′-(azetidin-3-yloxy)-2′,6′-dimethylbiphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetic acid 16 (65 mg, yield 95.6%) as a light yellow 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 silica gel column chromatography with elution system B

Sources & evidence

ORD record
ord-550d3e0dee504bc1841efa63f1ed957e
Source dataset
uspto-grants-2015_09
Patent number
US09139548B2

Reaction notes

Loading…