Methanol → HCID 59381898, compound

HRID 453370Notes

Reaction equation

HRID 453370 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[NH:12][C:13](=[O:22])[C:14]1[CH:19]=[CH:18][C:17]([CH3:20])=[C:16](I)[CH:15]=1.[CH3:23][OH:24].C(N(CC)CC)C.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CN([CH:64]=[O:65])C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[NH:12][C:13]([C:14]1[CH:19]=[CH:18][C:17]([CH3:20])=[C:16]([CH:15]=1)[C:23]([O:65][CH3:64])=[O:24])=[O:22]

Participants

7

Reactant 5

HCID 887MethanolHCID 6228DimethylformamideHCID 8471Triethylamine2×HCID 812191,3-Bis(diphenylphosphino)propane2×HCID 59381870HCID 59381870, compound

Product 1

HCID 59381898HCID 59381898, compound

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst2×

Procedure

A stainless steel cylinder equipped with a glass liner was charged with N-(2-fluoro-5-(trifluoromethyl)phenyl)-3-iodo-4-methylbenzamide 34 (1.089 g, 2.57 mmol), methanol (20 mL), and a magnetic stir bar. Argon gas was bubbled through this solution for one minute, and then triethylamine (0.358 ml, 2.57 mmol), 1,3-bis(diphenylphosphino)propane (0.0584 g, 0.142 mmol), and palladium(II) acetate (0.0289 g, 0.129 mmol) were added. The cylinder was sealed, charged to 200 psi of CO gas, placed into an oil bath at 75° C. and stirred for 2 hours. The reaction was cooled to room temperature, and palladium(II) acetate (0.0289 g, 0.129 mmol), DMF (2 mL), 1,3-bis(diphenylphosphino)propane (0.0584 g, 0.142 mmol), and triethylamine (0.358 ml, 2.57 mmol) were added. The cylinder was sealed, charged to 200 psi of CO gas, placed into an oil bath at 75° C. and stirred 48 hours. The reaction mixture was cooled to room temperature and concentrated. The residue was purified via column chromatography on silica gel (gradient elution 0 to 100% ethylacetate in hexane) to afford methyl 5-((2-fluoro-5-(trifluoromethyl)phenyl)carbamoyl)-2-methylbenzoate 35 as pale yellow solid. MS m/z found 356 [MH+]; calc. for C17H13F4NO3=355.28.

Workup

  1. customArgon gas was bubbled through this solution for one minute
  2. customThe cylinder was sealed
  3. additioncharged to 200 psi of CO gas
  4. customplaced into an oil bath at 75° C.
  5. customThe cylinder was sealed
  6. additioncharged to 200 psi of CO gas
  7. customplaced into an oil bath at 75° C.
  8. stirringstirred 48 hours
  9. temperatureThe reaction mixture was cooled to room temperature
  10. concentrationconcentrated
  11. customThe residue was purified via column chromatography on silica gel (gradient elution 0 to 100% ethylacetate in hexane)

Sources & evidence

ORD record
ord-b691a994c07f44f8806fa2228fe52b62
Source dataset
uspto-grants-2013_07
Patent number
US08492404B2

Reaction notes

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