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

HRID 2224278Notes

Reaction equation

HRID 2224278 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.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CCO.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>[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

6

Reactant 3

HCID 10340Sodium CarbonateHCID 742994-Chlorophenylboronic acidHCID 135262132-Benzyl-5-chloro-4-methoxypyridazin-3(2H)-one2×

Product 1

HCID 569275222-benzyl-5-(4-chlorophenyl)-4-methoxypyridazin-3(2H)-oneYield 83%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 21863594Toluene ethanolSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 2-benzyl-5-chloro-4-methoxypyridazin-3(2H)-one (20 g, 80 mmol) and 4-chlorophenylboronic acid (15.6 g, 100 mmol) in toluene/EtOH (2:1, 600 mL) at RT under argon was added (Ph3P)4Pd (1.85 g, 1.8 mmol) and 2 M aqueous Na2CO3 solution (160 mL, 320 mmol). The resulting suspension was heated at 90° C. for 16 h with stirring. HPLC/MS indicated about 4% of the 2-benzyl-5-chloro-4-methoxypyridazin-3(2H)-one still remained. After cooling the reaction mixture to RT, the solution was extracted with CH2Cl2 (2×150 mL). The combined organic layers were dried (Na2SO4), filtered and concentrated under vacuum. The crude product was purified by silica gel column chromatography (ISCO) eluting with hexanes/EtOAc to obtain pure title compound, 2-Benzyl-5-(4-chlorophenyl)-4-methoxypyridazin-3(2H)-one, (21.7 g, 83%) as a white solid. MS [M+H]+ 327; HPLC retention time=3.85 min.

Workup

  1. temperatureAfter cooling the reaction mixture to RT
  2. extractionthe solution was extracted with CH2Cl2 (2×150 mL)
  3. dry with materialThe combined organic layers were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customThe crude product was purified by silica gel column chromatography (ISCO)
  7. washeluting with hexanes/EtOAc

Sources & evidence

ORD record
ord-4745776979814042a16b71a1b2b7d3f8
Source dataset
uspto-grants-2008_05
Patent number
US07378418B2

Reaction notes

Loading…