Potassium Carbonate → Azoxystrobin

HRID 1859230Notes

Reaction equation

HRID 1859230 reaction equation
Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([O:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2/[C:15](=[CH:20]\[O:21][CH3:22])/[C:16]([O:18][CH3:19])=[O:17])[CH:3]=1.[C:23]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[OH:31])#[N:24].C(=O)([O-])[O-].[K+].[K+].[F-].[K+]>CN(C)C=O.O.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[C:23]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[O:31][C:2]1[N:7]=[CH:6][N:5]=[C:4]([O:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2/[C:15](=[CH:20]\[O:21][CH3:22])/[C:16]([O:18][CH3:19])=[O:17])[CH:3]=1)#[N:24]

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 119072-HydroxybenzonitrileHCID 522689Potassium FluorideHCID 11782200Methyl (2E)-2-(2-((6-chloropyrimidin-4-yl)oxy)phenyl)-3-methoxyprop-2-enoate2×

Product 1

HCID 3034285Azoxystrobin

Reagents, catalysts & solvents 4

HCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

(E)-methyl 2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxypropenoate in N,N-dimethylformamide (256.8 g, 33.69% strength) was vacuum distilled to remove the solvent. A solution of the potassium salt of 2-cyanophenol was then prepared by mixing 2-cyanophenol (37.0 g) and potassium carbonate (56.7 g) in water (209 g). This solution was added to the (E)-methyl 2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxypropenoate melt, which had previously been cooled to 80° C. Potassium fluoride (11.1 g) and tetrabutylammonium bromide (16.1 g) was then added to the reaction solution. The resulting mixture was stirred at 100° C. for 23 hours. Any distillates were allowed to come off under atmospheric conditions. Toluene and a further quantity of water was added to the solution. The organic layer was then separated. Toluene was removed from the organic phase by vacuum distillation (100° C., 20 mmHg). The melt was cooled to 90° C. after which methanol (108 ml) was added to help cooling to 65-75° C. The resulting mixture was cooled to 40° C. and kept at this temperature for 2 hours. It was then further cooled to 0-5° C. and held for another 1 hour period. The mixture was filtered to leave (E)-methyl 2-[2-(6-(2-cyanophenoxy)pyrimidin-4-yloxy)phenyl]-3-methoxypropenoate as the residue (67.0% isolated yield).

Workup

  1. distillationdistilled
  2. customto remove the solvent
  3. customA solution of the potassium salt of 2-cyanophenol was then prepared
  4. customThe organic layer was then separated
  5. customToluene was removed from the organic phase by vacuum distillation (100° C., 20 mmHg)
  6. temperatureThe melt was cooled to 90° C. after which methanol (108 ml)
  7. additionwas added
  8. temperatureto help cooling to 65-75° C
  9. temperatureThe resulting mixture was cooled to 40° C.
  10. waitkept at this temperature for 2 hours
  11. temperatureIt was then further cooled to 0-5° C.
  12. waitheld for another 1 hour period
  13. filtrationThe mixture was filtered

Sources & evidence

ORD record
ord-3c77ddd1d15044d78deba3c9066f6ad5
Source dataset
uspto-grants-2000_11
Patent number
US06153750

Reaction notes

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