Sodium Carbonate → (2'-Ethyl-5-fluoro-biphenyl-2-yloxy)-acetic acid

HRID 2250884Notes

Reaction equation

HRID 2250884 reaction equation
C([O:5][C:6](=[O:17])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=1Br)(C)(C)C.C([O-])([O-])=O.[Na+].[Na+].[CH2:24]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1B(O)O)[CH3:25]>COCCOC>[CH2:24]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[C:10]1[CH:11]=[C:12]([F:15])[CH:13]=[CH:14][C:9]=1[O:8][CH2:7][C:6]([OH:5])=[O:17])[CH3:25]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 41008622-Ethylphenylboronic Acid (contains varying amounts of Anhydride)HCID 59642165Tert-butyl (2-bromo-4-fluorophenoxy)acetate

Product 1

HCID 58689898(2'-Ethyl-5-fluoro-biphenyl-2-yloxy)-acetic acidYield 69.6%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of (2-bromo-4-fluoro-phenoxy)-acetic acid-t-butyl ester (2.00 g, 6.55 mmol) in DME (16 ml)/2M Na2CO3 (11.46 ml, 22.93 mmol) was treated with 2-ethylphenylboronic acid (1.96 g, 13.10 mmol), and Pd[PPh3]4 (757 mg, 0.655 mmol) in a microwave oven at 150° C. for 10 min. The reaction mixture was partitioned between water and ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated. The crude was absorbed on silica and purified on a silica gel column with a 5-20% ethyl acetate/hexanes gradient to afford 1.25 g of colorless oil (t-butyl ester). This material was dissolved in 4N HCl/dioxane (10 ml) and stirred at rt overnight. Concentration under reduced pressure afforded the product as colorless oil (1.08 g, 60%).

Workup

  1. customThe reaction mixture was partitioned between water and ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude was absorbed on silica
  7. custompurified on a silica gel column with a 5-20% ethyl acetate/hexanes gradient

Sources & evidence

ORD record
ord-25dd160ed74042b98b3b0240bfc22478
Source dataset
uspto-grants-2008_01
Patent number
US07317125B2

Reaction notes

Loading…