Triphenylphosphine → 2,4-Dichloro-6-cyclopropylbenzylamine

HRID 1051935Notes

Reaction equation

HRID 1051935 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+].C1C=CC(P([C:43]2[CH:48]=[CH:47]C=CC=2)C2C=CC=CC=2)=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 soln. 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), PPh3 (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 comb. org. layers were dried over MgSO4 and conc. 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 aq. phase was basified with 1M NaOH soln. and extracted 3 times with EtOAc. The comb. org. layers were dried over MgSO4 and conc. 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 materiallayers were dried over MgSO4 and conc. in vacuo
  6. customto give a crude white solid
  7. stirringAfter stirring at RT for 30 min
  8. extractionand extracted 3 times with EtOAc
  9. dry with materiallayers were dried over MgSO4 and conc. Purification with CC (KP-NH™ from Biotage)

Sources & evidence

ORD record
ord-427403c4bc0c42fc82eaed24af8cfec5
Source dataset
uspto-grants-2016_07
Patent number
US09388197B2

Reaction notes

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