Potassium Phosphate, Tribasic → 4-Cyclopropyl-2-fluoroaniline

HRID 1433797Notes

Reaction equation

HRID 1433797 reaction equation
Br[C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([F:9])[CH:3]=1.[CH:10]1(B(O)O)[CH2:12][CH2:11]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:10]1([C:2]2[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([F:9])[CH:3]=2)[CH2:12][CH2:11]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 1230504-Bromo-2-fluoroanilineHCID 2760897Cyclopropylboronic acid

Product 1

HCID 201000714-Cyclopropyl-2-fluoroanilineYield 45%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

(According to the procedure of D. Wallace and C. Chen, Tetrahedron Lett., 43, 6987 (2002)) 4-Bromo-2-fluoroaniline (19.0 g, 100 mmol) was reacted with cyclopropyl boronic acid (11.3 g, 131 mmol), palladium(II) acetate (1.12 g, 4.79 mmol), tricyclohexyl phosphine (2.80 g, 13.2 mmol), and potassium phosphate (74.2 g, 265 mmol) in toluene (400 mL) and water (30 mL). The mixture was heated in an oil bath at 100° C. for 2 days, cooled, and the liquid was filtered through a pad of celite. The residual solid in the reaction vessel was triturated with water (200 mL), and the suspension was filtered through celite. The aqueous filtrate was extracted once with hexanes (100 mL), the combined organic layers were dried over anhydrous magnesium sulfate. The dried organic layers were filtered through a silica gel pad, and the pad was washed with 80% v/v dichloromethane in hexanes (250 mL). The filtrates were concentrated in vacuo to give a red oil that was fractionally distilled (Vigreux column, 6 plates). The fraction distilling between 65-73° C. at 6-7 mbar was collected to give 6.8 g (45 mmol, 45%) of 4-cyclopropyl-2-fluoroaniline as a pale yellow liquid.

Workup

  1. temperaturecooled
  2. filtrationthe liquid was filtered through a pad of celite
  3. customThe residual solid in the reaction vessel was triturated with water (200 mL)
  4. filtrationthe suspension was filtered through celite
  5. extractionThe aqueous filtrate was extracted once with hexanes (100 mL)
  6. dry with materialthe combined organic layers were dried over anhydrous magnesium sulfate
  7. filtrationThe dried organic layers were filtered through a silica gel pad
  8. washthe pad was washed with 80% v/v dichloromethane in hexanes (250 mL)
  9. concentrationThe filtrates were concentrated in vacuo
  10. customto give a red oil that
  11. distillationwas fractionally distilled (Vigreux column, 6 plates)
  12. distillationThe fraction distilling between 65-73° C. at 6-7 mbar
  13. customwas collected

Sources & evidence

ORD record
ord-92f56f9d37e343b2a2cf539e3bfa045b
Source dataset
uspto-grants-2009_11
Patent number
US07612212B2

Reaction notes

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