2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → 3,4-bis(Benzyloxy)-6-[(4-fluorophenyl)methyl]pyridazine

HRID 927102Notes

Reaction equation

HRID 927102 reaction equation
[CH2:1]([O:8][C:9]1[N:10]=[N:11][C:12](Cl)=[CH:13][C:14]=1[O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[Br-].[F:59][C:60]1[CH:67]=[CH:66][C:63]([CH2:64][Zn+])=[CH:62][CH:61]=1>O1CCCC1.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([O:8][C:9]1[N:10]=[N:11][C:12]([CH2:64][C:63]2[CH:66]=[CH:67][C:60]([F:59])=[CH:61][CH:62]=2)=[CH:13][C:14]=1[O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 122134743,4-Bis(benzyloxy)-6-chloropyridazine2×HCID 178505763HCID 178505763, compound

Product 1

HCID 712704273,4-bis(Benzyloxy)-6-[(4-fluorophenyl)methyl]pyridazineYield 97%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 3,4-bis(benzyloxy)-6-chloropyridazine (Intermediate 1) (1 g, 3.06 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.117 g, 0.245 mmol) and palladium (II) acetate (0.027 g, 0.122 mmol) in tetrahydrofuran (6.12 ml) under nitrogen was added (4-fluorobenzyl)zinc(II) bromide (9.18 ml, 4.59 mmol) and the resulting red/brown mixture was heated at 65° C. for 24 hours. The reaction mixture was cooled, diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate solution, saturated ammonium chloride solution and brine. The organics were dried (MgSO4), filtered and solvent removed in vacuo to give a brown oil. The oil was purified by silica chromatography (eluting with 0-100% ethyl acetate in petrol) to yield the title compound (663 mg, 1.61 mmol, 97% yield).

Workup

  1. temperatureThe reaction mixture was cooled
  2. washwashed with saturated aqueous sodium bicarbonate solution, saturated ammonium chloride solution and brine
  3. dry with materialThe organics were dried (MgSO4)
  4. filtrationfiltered
  5. customsolvent removed in vacuo
  6. customto give a brown oil
  7. customThe oil was purified by silica chromatography (eluting with 0-100% ethyl acetate in petrol)

Sources & evidence

ORD record
ord-79d2a819b452424ea811f23102e76484
Source dataset
uspto-grants-2016_03
Patent number
US09290456B2

Reaction notes

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