Sodium Methoxide → 1-Methylethyl 2-chloro-4-fluoro-5-(2-methoxy-6-oxo-4-(pentafluoroethyl)-1(6H)-pyrimidinyl)benzoate

HRID 1193870Notes

Reaction equation

HRID 1193870 reaction equation
[Cl:1][C:2]1[CH:13]=[C:12]([F:14])[C:11]([N:15]2[C:20](=[O:21])[CH:19]=[C:18]([C:22]([F:28])([F:27])[C:23]([F:26])([F:25])[F:24])[N:17]=[C:16]2Cl)=[CH:10][C:3]=1[C:4]([O:6][CH:7]([CH3:9])[CH3:8])=[O:5].ClC1C=C(F)C(N2C(Cl)=CC(C(F)(F)C(F)(F)F)=NC2=O)=CC=1[C:33](OC(C)C)=[O:34].C[O-].[Na+]>CO>[Cl:1][C:2]1[CH:13]=[C:12]([F:14])[C:11]([N:15]2[C:20](=[O:21])[CH:19]=[C:18]([C:22]([F:28])([F:27])[C:23]([F:24])([F:25])[F:26])[N:17]=[C:16]2[O:34][CH3:33])=[CH:10][C:3]=1[C:4]([O:6][CH:7]([CH3:9])[CH3:8])=[O:5]

Participants

5

Reactant 3

HCID 10942334Sodium MethoxideHCID 21270698HCID 21270698, compoundHCID 21270787HCID 21270787, compound

Product 1

HCID 1354011-Methylethyl 2-chloro-4-fluoro-5-(2-methoxy-6-oxo-4-(pentafluoroethyl)-1(6H)-pyrimidinyl)benzoate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
25 °C

Procedure

The residue, a mixture of isopropyl 2-chloro-5-[2-chloro-6-oxo-4-pentafluoroethyl -1(6H)-pyrimidinyl]-4-fluorobenzoate and isopropyl 2-chloro-5-[6-chloro-2-oxo-4-pentafluoroethyl -1(2H)-pyrimidinyl]-4-fluorobenzoate, is dissolved in 20 ml of methanol and 3.8 ml of a 2N sodium methylate solution are added to the solution while stirring at 25° C. The temperature of the reaction mixture rises to 30° C. The mixture is subsequently stirred for 30 minutes and evaporated to dryness under reduced pressure. The residue is separated by chromatography on a silica gel column using n-hexane/diethyl ether (3:1). The first fraction, which still contains some diethylaniline, is dissolved in diethyl ether and the solution is extracted with 2N hydrochloric acid, washed to neutrality with water and dried over anhydrous sodium sulphate. The organic phase is evaporated to dryness under reduced pressure and the residue is recrystallized from n-hexane. There is obtained isopropyl 2-chloro-4-fluoro-5-[2-methoxy-6-oxo-4-pentafluoroethyl-1(6H)-pyrimidinyl]-benzoate, m.p. 82°-84° C. By further elution of the column with n-hexane/diethyl ether (1:2) there is obtained a second fraction which is recrystallized from diethyl ether/n-hexane. In this manner there is also obtained isopropyl 2-chloro-4-fluoro-5-[6-methoxy-2-oxo-4-pentafluoroethyl -1(2H)-pyrimidinyl]-benzoate, m.p. 127°-129° C.

Workup

  1. customrises to 30° C
  2. stirringThe mixture is subsequently stirred for 30 minutes
  3. customevaporated to dryness under reduced pressure
  4. customThe residue is separated by chromatography on a silica gel column
  5. dissolutionis dissolved in diethyl ether
  6. extractionthe solution is extracted with 2N hydrochloric acid
  7. washwashed
  8. dry with materialdried over anhydrous sodium sulphate
  9. customThe organic phase is evaporated to dryness under reduced pressure
  10. customthe residue is recrystallized from n-hexane

Sources & evidence

ORD record
ord-e1ea0a3fa2344c468e69bb7cfec32a26
Source dataset
uspto-grants-1989_03
Patent number
US04812164

Reaction notes

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