Potassium Phosphate, Tribasic → 4-Chloro-2-cyclopropyl-5-methoxyaniline

HRID 705370Notes

Reaction equation

HRID 705370 reaction equation
Br[C:2]1[CH:8]=[C:7]([Cl:9])[C:6]([O:10][CH3:11])=[CH:5][C:3]=1[NH2:4].[CH:12]1(B(O)O)[CH2:14][CH2:13]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[Cl:9][C:7]1[C:6]([O:10][CH3:11])=[CH:5][C:3]([NH2:4])=[C:2]([CH:12]2[CH2:14][CH2:13]2)[CH:8]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 147747832-Bromo-4-chloro-5-methoxyaniline

Product 1

HCID 679818004-Chloro-2-cyclopropyl-5-methoxyaniline

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

A mixture of Example 18A (1.0 equivalents), cyclopropyl boronic acid (1.1 equivalents), tricyclohexylphosphine (0.05 equivalents), palladium acetate (0.025 equivalents) and K3PO4 (2 equivalents) in a 20:1 volume ratio of toluene and water was sparged with nitrogen for 15 minutes. The reaction mixture was then heated to 100° C. for 12 hours, cooled, diluted with water, stirred for 1 hour and filtered through a diatomaceous earth pad, and the pad was rinsed with toluene. The filtrate was mixed and the layers were separated. The organic layer was washed with water and saturated brine, dried (Na2SO4), filtered and concentrated to an oil that was used without further purification.

Workup

  1. temperaturecooled
  2. filtrationfiltered through a diatomaceous earth pad
  3. washthe pad was rinsed with toluene
  4. additionThe filtrate was mixed
  5. customthe layers were separated
  6. washThe organic layer was washed with water and saturated brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated to an oil that
  10. customwas used without further purification

Sources & evidence

ORD record
ord-16c24fb3fd994b17a23e486d2fc38b36
Source dataset
uspto-grants-2015_11
Patent number
US09173887B2

Reaction notes

Loading…