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

HRID 404323Notes

Reaction equation

HRID 404323 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+].N#N>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.CCOC(C)=O>[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

8

Reactant 4

HCID 947NitrogenHCID 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 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of ethyl 3-chloro-4-(trifluoromethylsulfonyloxy)benzoate T2.4 (3.00 g, 9.02 mmol), 2-fluoro-5-methoxyphenylboronic acid (commercially available from Sigma-Aldrich, St. Louis, Mo., USA) (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 chromatography (eluent with hexane/EtOAc; 85/15) to give T2.5. 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. temperatureThe reaction was cooled to room temperature
  2. washThe mixture was then washed with brine (30×4 mL)
  3. dry with materialThe organic layer was dried over MgSO4
  4. customThe residue was purified by CombiFlash® silica gel column chromatography (eluent with hexane/EtOAc; 85/15)
  5. customto give T2.5

Sources & evidence

ORD record
ord-2e299561a20f4f19881a77e83a9ad52e
Source dataset
uspto-grants-2014_06
Patent number
US08748462B2

Reaction notes

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