Potassium Carbonate → Ethyl 2-chloro-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-carboxylate

HRID 2098900Notes

Reaction equation

HRID 2098900 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][C:12]=1OS(C(F)(F)F)(=O)=O)[C:5]([O:7][CH2:8][CH3:9])=[O:6].[F:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][C:23]=1B(O)O.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH:10]=[CH:11][C:12]=1[C:23]1[CH:24]=[C:25]([O:28][CH3:29])[CH:26]=[CH:27][C:22]=1[F:21]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 41572112-Fluoro-5-methoxyphenylboronic acidHCID 57467588Ethyl 3-chloro-4-(trifluoromethylsulfonyloxy)benzoate

Product 1

HCID 57706474Ethyl 2-chloro-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-carboxylate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A reaction mixture of ethyl 3-chloro-4-(trifluoromethylsulfonyloxy)benzoate (T1.5) (3.00 g, 9.02 mmol), 2-fluoro-5-methoxyphenylboronic acid (commercially available from Aldrich) (1.84 g, 10.8 mmol), tetrakis(triphenylphosphine)palladium (0.521 g, 0.451 mmol) and potassium carbonate (2.49 g, 18.0 mmol) in DMF (20 mL), was purged with N2 three times and then heated at 100° C. for 4 hours. The reaction was cooled to room temperature, and EtOAc (130 mL) was added. The mixture was then washed with brine (30×4 mL). The organic layer was dried over MgSO4. The residue was purified by CombiFlash® silica gel column (eluting with hexane/EtOAc; 85/15) to give T1.6. 1H NMR (400 MHz, CDCl3) δ ppm 8.08 (d, 1H), 7.90 (d, 1H), 7.33 (dd, 1H), 6.96-7.02 (m, 1H), 6.82-6.85 (m, 1H), 6.74 (d, 1H), 4.33 (q, 2H), 4.31 (s, 3H), 1.34 (t, 3H). MS ESI (pos.) m/e: 309.1 (M+H)+.

Workup

  1. customwas purged with N2 three times
  2. temperatureThe reaction was cooled to room temperature
  3. additionEtOAc (130 mL) was added
  4. washThe mixture was then washed with brine (30×4 mL)
  5. dry with materialThe organic layer was dried over MgSO4
  6. customThe residue was purified by CombiFlash® silica gel column (eluting with hexane/EtOAc; 85/15)
  7. customto give T1.6

Sources & evidence

ORD record
ord-a3c25c48f0284bdba9be4cf66717461a
Source dataset
uspto-grants-2013_05
Patent number
US08450522B2

Reaction notes

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