Sodium Carbonate → 1,3-Diethyl 2-[2'-chloro-4'-(trifluoromethyl) [1,1'-biphenyl]-3-yl]propanedioate

HRID 628473Notes

Reaction equation

HRID 628473 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:8]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH:5]=[CH:6][CH:7]=1.[Cl:19][C:20]1[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][C:21]=1B(O)O.O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[Cl:19][C:20]1[CH:25]=[C:24]([C:26]([F:27])([F:28])[F:29])[CH:23]=[CH:22][C:21]=1[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH:8]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH:3]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 2783251[2-Chloro-4-(trifluoromethyl)phenyl]boronic acidHCID 12797953Diethyl (3-bromophenyl)malonate

Product 1

HCID 669736161,3-Diethyl 2-[2'-chloro-4'-(trifluoromethyl) [1,1'-biphenyl]-3-yl]propanedioateYield 64.8%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

Diethyl 2-(3-bromophenyl)propanedioate (3.75 g), 2-chloro-4-(trifluoromethyl)phenyl boronic acid (4.0 g), dioxane (10 mL), 2M aqueous sodium carbonate solution (5 mL) and dichlorobis(triphenylphosphine)palladium(II) (422 mg) were added to a vial, and the reaction mixture was heated at 80° C. for 30 minutes. The reaction mixture was then cooled, poured into water, extracted with ethyl acetate, and the organic phase was separated and concentrated under vacuum in the presence of Celite® (diatomaceous earth) to yield a crude solid. The crude solid was purified by medium pressure liquid chromatography on silica gel eluting with a gradient of ethyl acetate in hexanes to yield 3.2 g of the title compound. 1H NMR (CDCl3) δ 7.74 (s, 1H), 7.57 (d, 1H), 7.37-7.50 (m, 5H), 4.57 (s, 1H), 4.23 (q, 4H), 1.27 (t, 6H).

Workup

  1. temperatureThe reaction mixture was then cooled
  2. extractionextracted with ethyl acetate
  3. customthe organic phase was separated
  4. concentrationconcentrated under vacuum in the presence of Celite® (diatomaceous earth)
  5. customto yield a crude solid
  6. customThe crude solid was purified by medium pressure liquid chromatography on silica gel eluting with a gradient of ethyl acetate in hexanes

Sources & evidence

ORD record
ord-9227008b77a840cfa73928ce38377e87
Source dataset
uspto-grants-2016_04
Patent number
US09314025B2

Reaction notes

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