Reaction #896

Reaction equation

NaH

4-chloro-2-(methylthio)pyrimidine

3-(trifluoromethyl)phenol

→

phenoxide

2-methylthio-4-[3-(trifluoromethyl)phenoxy]pyrimidine

Solvents

THF

Conditions

Workup

1. 1
   workup.ADDITIONVII-1) (3.0 g, 0.0187 mol) was added
2. 2
   Temperaturethe mixture was refluxed for about 10 hours
3. 3
   OtherThe reaction solution was partitioned between ethyl acetate and aqueous saturated sodium hydrogen carbonate
4. 4
   Otherto separate an organic phase
5. 5
   WashThe organic phase was washed with aqueous saturated sodium chloride
6. 6
   Dryingdried over anhydrous sodium sulfate
7. 7
   Concentrationconcentrated
8. 8
   Otherrecrystallized from a methanol/water system
9. 9
   Otherto obtain the intermediate compound

Procedure

In THF, a phenoxide was prepared from 3-(trifluoromethyl)phenol (4.54 g, 0.0187×1.5 mol) was mixed with NaH (1.12 g (ca. 60% in mineral oil), 0.0187×1.5 mol), and 4-chloro-2-(methylthio)pyrimidine (Compound No. VII-1) (3.0 g, 0.0187 mol) was added thereto and the mixture was refluxed for about 10 hours. The reaction solution was partitioned between ethyl acetate and aqueous saturated sodium hydrogen carbonate to separate an organic phase. The organic phase was washed with aqueous saturated sodium chloride, dried over anhydrous sodium sulfate and concentrated, then recrystallized from a methanol/water system to obtain the intermediate compound.

Source