Sodium Carbonate → Ethyl 2'-chloro-4'-(trifluoromethyl)[1,1'-biphenyl]-3-acetate

HRID 2365464Notes

Reaction equation

HRID 2365464 reaction equation
I[C:2]1[CH:3]=[C:4]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH:5]=[CH:6][CH:7]=1.[Cl:14][C:15]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][C:16]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1>O>[Cl:14][C:15]1[CH:20]=[C:19]([C:21]([F:22])([F:23])[F:24])[CH:18]=[CH:17][C:16]=1[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH:3]=1

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 2783251[2-Chloro-4-(trifluoromethyl)phenyl]boronic acidHCID 57581611Ethyl 2-(3-iodophenyl)acetate

Product 1

HCID 66973842Ethyl 2'-chloro-4'-(trifluoromethyl)[1,1'-biphenyl]-3-acetateYield 49.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Ethyl 3-iodophenylacetate (2.90 g), 2-chloro-4-(trifluoromethyl)phenyl boronic acid (3.3 g), 2M aqueous sodium carbonate solution (5 mL), dioxane (10 mL) and dichloro-bis(triphenylphosphine)palladium(II) (350 mg) were heated at 80° C. for 30 min with stirring. The reaction mixture was then cooled, poured into water, extracted with ethyl acetate, and the organic layer was separated and concentrated under vacuum in the presence of Celite® to a solid residue. This solid residue was purified by medium pressure liquid chromatography on silica gel eluting with a gradient of ethyl acetate in hexanes to yield 1.7 g of the title compound. 1H NMR (CDCl3) δ 7.14 (s, 1H), 7.56 (d, 1H) 7.30-7.45 (m, 5H), 4.77 (q, 2H), 3.67 (s, 2H), 1.26 (t, 3H).

Workup

  1. temperatureThe reaction mixture was then cooled
  2. extractionextracted with ethyl acetate
  3. customthe organic layer was separated
  4. concentrationconcentrated under vacuum in the presence of Celite® to a solid residue
  5. customThis solid residue was purified by medium pressure liquid chromatography on silica gel eluting with a gradient of ethyl acetate in hexanes

Sources & evidence

ORD record
ord-70408cc69f9e432d9c2465dd8a143d4b
Source dataset
uspto-grants-2014_04
Patent number
US08697707B2

Reaction notes

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