Tricyclohexylphosphine → 4-Chloro-5-cyclopropyl-2-methoxybenzenamine

HRID 588897Notes

Reaction equation

HRID 588897 reaction equation
[Cl:1][C:2]1[C:8](I)=[CH:7][C:5]([NH2:6])=[C:4]([O:10][CH3:11])[CH:3]=1.[CH:12]1(B(O)O)[CH2:14][CH2:13]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C1(C)C=CC=CC=1.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:1][C:2]1[C:8]([CH:12]2[CH2:14][CH2:13]2)=[CH:7][C:5]([NH2:6])=[C:4]([O:10][CH3:11])[CH:3]=1

Participants

7

Reactant 3

HCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 917583774-Chloro-5-iodo-2-methoxyaniline

Product 1

HCID 1176072014-Chloro-5-cyclopropyl-2-methoxybenzenamineYield 89.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 4-chloro-5-iodo-2-methoxyaniline (5.0 g, 17.6 mmol), cyclopropylboronic acid (1.8 g, 21.1 mmol), Pd(OAc)2 (314 mg, 1.4 mmol), tricyclohexylphosphine (500 mg, 17.6 mmol), K3PO4.3H2O (16.4 g, 61.6 mmol) in toluene (62.5 mL) and H2O (3 mL) was stirred at 80° C. under argon for 16 h. The mixture was allowed to cool to RT, and then partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate=10:1) to afford the desired product (3.1 g, 88.5% yield). ESI-MS m/z: 198.2[M+H]+.

Workup

  1. temperatureto cool to RT
  2. custompartitioned between ethyl acetate and water
  3. washThe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate=10:1)

Sources & evidence

ORD record
ord-08497bdcb85a4398acbab13183849aaa
Source dataset
uspto-grants-2016_01
Patent number
US09227978B2

Reaction notes

Loading…