Reaction #67082

Reaction equation

chloro(3-chlorobenzyl)zinc tetrahydrofuran

4-{[2-chloro-4-(trifluoromethyl)pyrimidin-5-yl]carbonyl}thiomorpholine 1,1-dioxide

tetrahydrofuran

→

4-{[2-(3-chlorobenzyl)-4-(trifluoromethyl)pyrimidin-5-yl]carbonyl}thiomorpholine 1,1-dioxide

Solvents

water

Conditions

Workup

1. 1
   Extractionthe aqueous layer was extracted with ethyl acetate
2. 2
   WashThe organic layer was washed with water and saturated brine
3. 3
   Dryingdried over anhydrous magnesium sulfate
4. 4
   Filtrationfiltered
5. 5
   Concentrationconcentrated
6. 6
   OtherThe obtained residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate)
7. 7
   workup.ADDITIONTo the obtained pale yellow solid were added 1,4-dioxane (10 mL) and 1-methylpiperazine (0.16 mL)
8. 8
   workup.STIRRINGby stirring at room temperature for 6 hours
9. 9
   workup.ADDITIONTo the reaction mixture was added water
10. 10
    Extractionthe aqueous layer was extracted with ethyl acetate
11. 11
    WashThe organic layer was washed with water and saturated brine
12. 12
    Dryingdried over anhydrous magnesium sulfate
13. 13
    Filtrationfiltered
14. 14
    Concentrationconcentrated
15. 15
    OtherThe obtained residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate)
16. 16
    WashThe obtained white solid was washed with ethanol

Procedure

To a mixture of 4-{[2-chloro-4-(trifluoromethyl)pyrimidin-5-yl]carbonyl}thiomorpholine 1,1-dioxide (500 mg), dichlorobis(triphenylphosphine)nickel (II) (190 mg), tetrahydrofuran (10 mL) was added a 0.5 M chloro(3-chlorobenzyl)zinc tetrahydrofuran solution (3.2 mL), followed by stirring at room temperature for 6 hours. To the reaction mixture was added water and the aqueous layer was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, then dried over anhydrous magnesium sulfate, filtered, and concentrated. The obtained residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate). To the obtained pale yellow solid were added 1,4-dioxane (10 mL) and 1-methylpiperazine (0.16 mL), followed by stirring at room temperature for 6 hours. To the reaction mixture was added water and the aqueous layer was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, then dried over anhydrous magnesium sulfate, filtered, and concentrated. The obtained residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate). The obtained white solid was washed with ethanol to obtain 4-{[2-(3-chlorobenzyl)-4-(trifluoromethyl)pyrimidin-5-yl]carbonyl}thiomorpholine 1,1-dioxide (212 mg) as a white solid.

Source