Toluene → Tert-butyl 2-(4-fluoroanilino)-4-(4-(hydroxymethyl)phenyl)benzoate

HRID 2191770Notes

Reaction equation

HRID 2191770 reaction equation
C1(C)C=CC=CC=1.Br[C:9]1[CH:21]=[CH:20][C:12]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[C:11]([NH:22][C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[CH:10]=1.[OH:30][CH2:31][C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1.C(=O)([O-])O.[Na+]>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.O.C(O)C>[F:29][C:26]1[CH:27]=[CH:28][C:23]([NH:22][C:11]2[CH:10]=[C:9]([C:35]3[CH:36]=[CH:37][C:32]([CH2:31][OH:30])=[CH:33][CH:34]=3)[CH:21]=[CH:20][C:12]=2[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[CH:24][CH:25]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 516892Sodium BicarbonateHCID 27347064-(Hydroxymethyl)benzeneboronic acidHCID 68956988Tert-butyl 4-bromo-2-(4-fluoroanilino)benzoate

Product 1

HCID 68962839Tert-butyl 2-(4-fluoroanilino)-4-(4-(hydroxymethyl)phenyl)benzoateYield 29.8%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×

Procedure

To toluene 4.0 mL solution of tert-butyl 4-bromo-2-(4-fluoroanilino)benzoate 0.20 g were added ethanol 1.2 mL, water 0.60 mL, 4-(hydroxymethyl)phenylboronic acid 91 mg, sodium hydrogen carbonate 0.12 g and tetrakis(triphenylphosphine)palladium(0) 35 mg at room temperature, and it was heated and refluxed under nitrogen atmosphere for 6 hours. After the reaction mixture was cooled to room temperature, water was added to it. The organic layer was separated and collected, dried over anhydrous magnesium sulfate after washing with saturated sodium chloride aqueous solution, and the solvent was removed under reduced pressure. The obtained residue was refined by silica gel column chromatography [Fuji SILYSIA Chemical Ltd., PSQ100B(spherical type), eluent; hexane:ethyl acetate=2:1] to give tert-butyl 2-(4-fluoroanilino)-4-(4-(hydroxymethyl)phenyl)benzoate 64 mg of a pale yellow solid.

Workup

  1. temperatureit was heated
  2. temperaturerefluxed under nitrogen atmosphere for 6 hours
  3. customThe organic layer was separated
  4. customcollected
  5. dry with materialdried over anhydrous magnesium sulfate
  6. washafter washing with saturated sodium chloride aqueous solution
  7. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-f010e1f543ba4e719aa86aff663411d2
Source dataset
uspto-grants-2012_12
Patent number
US08327467B2

Reaction notes

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