Reaction #897

Reaction equation

Ethanol

NaH

m-trifluoromethyl-phenol

NaH

4,6-dichloro-2-methylthiopyrimidine

→

4-ethoxy-2-methylthio-6-[3-(trifluoromethyl)phenoxy]pyrimidine

Solvents

THF

DMF

Conditions

Workup

1. 1
   workup.ADDITIONVII-23)(5.0 g, 0.0256 mol) was added
2. 2
   workup.ADDITIONwere added
3. 3
   TemperatureThe resulting solution was refluxed for about 7 hours
4. 4
   OtherThe reaction solution was partitioned between ethyl acetate and aqueous saturated sodium hydrogen carbonate
5. 5
   Otherto separate an organic phase
6. 6
   WashThe organic phase was washed with aqueous saturated sodium chloride
7. 7
   Dryingdried over anhydrous sodium sulfate
8. 8
   Concentrationconcentrated
9. 9
   Otherpurified on a silica gel column

Procedure

Ethanol (1.18 g, 0.0256×1.0 mol) and NaH (1.02 g, (ca.60% in mineral oil), 0.0256×1.0 mol) were dissolved in THF and 4,6-dichloro-2-methylthiopyrimidine (Compound No. VII-23)(5.0 g, 0.0256 mol) was added thereto. The resulting solution was stirred for about 30 minutes at room temperature. To this reaction solution, m-trifluoromethyl-phenol (6.23 g, 0.0256×1.5 mol), NaH (1.54 g, (ca.60% in mineral oil), 0.0256×1.5 mol), and KI (2.12 g, 0.0256×0.5 mol) dissolved in DMF were added. The resulting solution was refluxed for about 7 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, and thereafter purified on a silica gel column.

Source