Triphenylphosphine → 2,4-Dichloro-6-cyclopropylbenzylamine

HRID 1481330Notes

Reaction equation

HRID 1481330 reaction equation
Br[C:2]1[CH:19]=[C:18]([Cl:20])[CH:17]=[C:16]([Cl:21])[C:3]=1[CH2:4][N:5]1C(=O)C2C(=CC=CC=2)C1=O.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P([C:43]2[CH:48]=[CH:47]C=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(B(O)O)CC1.O.NN.[OH-].[Na+]>C1(C)C=CC=CC=1.O.CCO.CC([O-])=O.CC([O-])=O.[Pd+2].CCOC(C)=O>[Cl:21][C:16]1[CH:17]=[C:18]([Cl:20])[CH:19]=[C:2]([CH:47]2[CH2:48][CH2:43]2)[C:3]=1[CH2:4][NH2:5]

Participants

12

Reactant 6

HCID 11776TriphenylphosphineHCID 14798Sodium HydroxideHCID 24654Hydrazine hydrate (1:1)HCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acid2×HCID 897047582-(2-Bromo-4,6-dichlorobenzyl)isoindoline-1,3-dione

Product 1

HCID 897048402,4-Dichloro-6-cyclopropylbenzylamine

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalyst2×HCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 2-(2-bromo-4,6-dichlorobenzyl)isoindoline-1,3-dione (1.96 mmol) in 16 mL toluene and 0.8 mL water were added K3PO4 (6.85 mmol), triphenylphosphine (0.23 mmol), cyclopropylboronic acid (2.35 mmol) and Pd(OAc)2 (0.15 mmol). The mixture was stirred at 80° C. for 24 h when another portion of cyclopropylboronic acid (1.96 mmol) and Pd(OAc)2 (0.15 mmol) were added. The reaction mixture was stirred at 80° C. for further 4 days, cooled to RT, quenched with sat. aq. NaHCO3 solution and extracted with EtOAc. The combined organic layers were dried over MgSO4 and concentrated in vacuo to give a crude white solid. This solid was dissolved in 15 mL EtOH and 12.6 mL of hydrazine monohydrate was added. After stirring at RT for 30 min, EtOAc was added. The aqueous phase was basified with 1M NaOH solution and extracted 3 times with EtOAc. The combined organic layers were dried over MgSO4 and concentrated. Purification with CC (KP-NH™ from Biotage) gives the desired compound as red/brown oil.

Workup

  1. additionwere added
  2. temperaturecooled to RT
  3. customquenched with sat. aq. NaHCO3 solution
  4. extractionextracted with EtOAc
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customto give a crude white solid
  8. stirringAfter stirring at RT for 30 min
  9. extractionextracted 3 times with EtOAc
  10. dry with materialThe combined organic layers were dried over MgSO4
  11. concentrationconcentrated
  12. customPurification with CC (KP-NH™ from Biotage)

Sources & evidence

ORD record
ord-79b3840fde9c4f0090083f9abd171879
Source dataset
uspto-grants-2016_08
Patent number
US09409917B2

Reaction notes

Loading…