Cyclopropylboronic acid → 3-Cyclopropyl-4-fluoroaniline

HRID 880145Notes

Reaction equation

HRID 880145 reaction equation
[CH:1]1(B(O)O)[CH2:3][CH2:2]1.P(=O)([O-])[O-].[K+].[K+].Br[C:14]1[CH:15]=[C:16]([CH:18]=[CH:19][C:20]=1[F:21])[NH2:17]>O.C1(C)C=CC=CC=1.C([O-])(=O)C.C([O-])(=O)C.[Pd+2].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>[CH:1]1([C:14]2[CH:15]=[C:16]([CH:18]=[CH:19][C:20]=2[F:21])[NH2:17])[CH2:3][CH2:2]1

Participants

8

Reactant 3

HCID 2760897Cyclopropylboronic acidHCID 27792863-Bromo-4-fluoroanilineHCID 178527066HCID 178527066, compound

Product 1

HCID 574163033-Cyclopropyl-4-fluoroanilineYield 65.4%

Reagents, catalysts & solvents 4

HCID 75806TricyclohexylphosphineCatalystHCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

558 mg of cyclopropylboronic acid, 3.7 g of tribasic potassium phosphonate, 70 mg of tricyclohexylphosphane and 56 mg of palladium(2+) diacetate in 1.5 ml of water are added to a solution of 950 mg of 3-bromo-4-fluoroaniline in 20 ml of toluene, with stirring and under argon. The mixture is degassed and then heated to a temperature of 100° C. After 15 hours, the reaction medium is cooled to a temperature in the region of 20° C., run into 100 ml of water, and then extracted with four times 60 ml of diethyl ether. The combined organic phases are dried over anhydrous magnesium sulphate, filtered and concentrated under reduced pressure. The residue is purified on a silica column, eluent: 7030 cyclohexaneethyl acetate. 494 mg of 3-cyclopropyl-4-fluoroaniline are obtained in the form of a brown oil, the characteristics of which are the following:

Workup

  1. customThe mixture is degassed
  2. temperaturethe reaction medium is cooled to a temperature in the region of 20° C.
  3. extractionextracted with four times 60 ml of diethyl ether
  4. dry with materialThe combined organic phases are dried over anhydrous magnesium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue is purified on a silica column, eluent

Sources & evidence

ORD record
ord-af0b169222ca4ed9bbeb016d1134a47c
Source dataset
uspto-grants-2015_03
Patent number
US08993565B2

Reaction notes

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