Toluene → 2-benzyl-5-(4-chlorophenyl)-4-methoxypyridazin-3(2H)-one

HRID 1865831Notes

Reaction equation

HRID 1865831 reaction equation
[CH2:1]([N:8]1[C:13](=[O:14])[C:12]([O:15][CH3:16])=[C:11](Cl)[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:18][C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1.C1(C)C=CC=CC=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Na+].[Na+].CCO>[CH2:1]([N:8]1[C:13](=[O:14])[C:12]([O:15][CH3:16])=[C:11]([C:22]2[CH:23]=[CH:24][C:19]([Cl:18])=[CH:20][CH:21]=2)[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 1140TolueneHCID 742994-Chlorophenylboronic acidHCID 135262132-Benzyl-5-chloro-4-methoxypyridazin-3(2H)-one

Product 1

HCID 569275222-benzyl-5-(4-chlorophenyl)-4-methoxypyridazin-3(2H)-oneYield 100,986.297%

Reagents, catalysts & solvents 3

HCID 10340Sodium CarbonateCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
120 °C

Procedure

To a round bottom flask was added 2-benzyl-5-chloro-4-methoxypyridazin-3(2H)-one (25.1 gm, 0.1 mmol), 4-chlorophenyl boronic acid (17.215 gm, 0.11 mmol), Pd(PPh3)4(9.24 gm, 0.008 mmol), toluene (200 ml), EtOH (200 ml) and 2.0N Na2CO3 (200 ml, 0.4 mmol). The reaction was purged with argon for 10 min. The reaction was then heated to 120° C. and stirred at this temperature for 18 hrs. After this time, the reaction was cooled to rt, poured into a separatory funnel and the layers were separated. The aqueous layer was extracted with EtOAc (50 ml). The combined organic layers were washed with 1N NaOH (200 ml), water (200 ml) and saturated aqueous NaCl (200 ml). The organic layer was then slurried with MgSO4 to remove excess water, filtered and concentrated to give the crude product. The crude product was purified using an automated column chromatography system (ISCO, 330 gm silica gel) eluting with a gradient of 0-30% EtOAc/CH2Cl2 to give product 2-benzyl-5-(4-chlorophenyl)-4-methoxypyridazin-3(2H)-one (33 gm, 99% yield) as light yellow solid. HPLC retention time (method A) 3.740 min; LCMS (M+H)=327.2.

Workup

  1. customThe reaction was purged with argon for 10 min
  2. temperatureAfter this time, the reaction was cooled to rt
  3. additionpoured into a separatory funnel
  4. customthe layers were separated
  5. extractionThe aqueous layer was extracted with EtOAc (50 ml)
  6. washThe combined organic layers were washed with 1N NaOH (200 ml), water (200 ml) and saturated aqueous NaCl (200 ml)
  7. customto remove excess water
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give the crude product
  11. customThe crude product was purified
  12. washeluting with a gradient of 0-30% EtOAc/CH2Cl2

Sources & evidence

ORD record
ord-b382a18d96454e82bd33e4c83461ef2f
Source dataset
uspto-grants-2009_12
Patent number
US07629342B2

Reaction notes

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