Triphenylphosphine → 3-Cyclopropyl-4-fluoroaniline

HRID 2200195Notes

Reaction equation

HRID 2200195 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[F:9])[NH2:5].[CH:10]1(B(O)O)[CH2:12][CH2:11]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CC([O-])=O.CC([O-])=O.[Pd+2].O.C1(C)C=CC=CC=1>[CH:10]1([C:2]2[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=2[F:9])[NH2:5])[CH2:12][CH2:11]1

Participants

8

Reactant 4

HCID 11776TriphenylphosphineHCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 27792863-Bromo-4-fluoroaniline

Product 1

HCID 574163033-Cyclopropyl-4-fluoroanilineYield 61%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

Mix 3-bromo-4-fluoro-aniline (415 mg, 2.18 mmol), cyclopropylboronic acid (244 mg, 2.84 mmol), K3PO4 (1.62 g, 7.64 mmol), triphenylphosphine (61 mg, 0.22 mmol), Pd(OAc)2 (25 mg, 0.11 mmol), toluene (12 mL) and water (1 mL) under N2, stir at 100° C. for 16 hrs. Cool the reaction to 25° C., add water (10 mL), extract with EtOAc (10 mL×2). Combine the organic layers; wash with brine (15 mL), dry over anhydrous Na2SO4. Concentrate under reduced pressure to give the crude product. Purification by chromatography (silica gel, PE:EtOAc=2:1) affords the target compound (200 mg, 61%).

Workup

  1. temperatureCool
  2. customthe reaction to 25° C.
  3. extractionextract with EtOAc (10 mL×2)
  4. washwash with brine (15 mL)
  5. dry with materialdry over anhydrous Na2SO4
  6. concentrationConcentrate under reduced pressure
  7. customto give the crude product
  8. customPurification by chromatography (silica gel, PE:EtOAc=2:1)

Sources & evidence

ORD record
ord-b10a07cf608e4b23bf327d36fd33a9c9
Source dataset
uspto-grants-2016_06
Patent number
US09359338B2

Reaction notes

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