Water → HCID 131727401, compound

HRID 2110280Notes

Reaction equation

HRID 2110280 reaction equation
FC(F)(F)S(O[C:7]1[CH:12]=[CH:11][C:10]([C:13]#[N:14])=[C:9]([F:15])[C:8]=1[F:16])(=O)=O.[C:19]([NH:26][C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][C:28]=1[F:36])([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20].C(=O)([O-])[O-].[Na+].[Na+].O>O1CCOCC1.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>[C:22]([O:21][C:19](=[O:20])[NH:26][C:27]1[CH:32]=[CH:31][C:30]([C:7]2[CH:12]=[CH:11][C:10]([C:13]#[N:14])=[C:9]([F:15])[C:8]=2[F:16])=[CH:29][C:28]=1[F:36])([CH3:25])([CH3:23])[CH3:24]

Participants

7

Reactant 4

HCID 962Water2×HCID 10340Sodium CarbonateHCID 22288677{4-[(tert-Butoxycarbonyl)amino]-3-fluorophenyl}boronic acidHCID 57636526HCID 57636526, compound

Product 1

HCID 131727401HCID 131727401, compoundYield 16.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A solution of 3.75 g of 4-cyano-2,3-difluorophenyl trifluoromethanesulfonate in 220 mL of dioxane is admixed at ambient temperature with 5 g of N-Boc-4-amino-3-fluorophenylboronic acid, 3.87 g of sodium carbonate in solution with 56 mL of distilled water and then 1.81 g of tetrakistriphenylphosphinepalladium. The reaction mixture is heated for 3 h at reflux and then poured, after cooling, into the distilled water. This mixture is extracted with ethyl acetate, the organic phase is decanted, washed a number of times with distilled water, then with saturated aqueous sodium chloride solution, dried over magnesium sulfate and then concentrated to dryness under reduced pressure. The solid obtained is chromatographed on a silica column (eluent: cyclohexane/ethyl acetate, 90/10 by volume). Evaporation to dryness under reduced pressure of the fractions containing the expected product gives 0.75 g of tert-butyl(4′-cyano-3,2′,3′-trifluorobiphenyl-4-yl)carbamate in the form of a pale pink solid, whose characteristics are as follows:

Workup

  1. temperatureThe reaction mixture is heated for 3 h
  2. temperatureat reflux
  3. additionpoured
  4. extractionThis mixture is extracted with ethyl acetate
  5. customthe organic phase is decanted
  6. washwashed a number of times with distilled water
  7. dry with materialwith saturated aqueous sodium chloride solution, dried over magnesium sulfate
  8. concentrationconcentrated to dryness under reduced pressure
  9. customThe solid obtained
  10. customis chromatographed on a silica column (eluent: cyclohexane/ethyl acetate, 90/10 by volume)
  11. customEvaporation to dryness under reduced pressure of the fractions
  12. additioncontaining the expected product

Sources & evidence

ORD record
ord-a6f6af1fccd64d249d434cda7bad0c78
Source dataset
uspto-grants-2009_04
Patent number
US07517902B2

Reaction notes

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