Reaction #1551

Reaction equation

phosphorous pentoxide

2-phenyl-6-trifluoromethyl-4(3H)-pyrimidinone

dimethoxymethane

phosphorous pentoxide

sodium hydroxide

→

3-methoxymethyl-2-phenyl-6-trifluoromethyl-4(3H)-pyrimidinone

Yield 32.8%

Solvents

chloroform

methylene chloride

hexane

ethyl acetate

Conditions

Workup

1. 1
   Otherat room temperature
2. 2
   workup.ADDITIONThe reaction mixture was poured
3. 3
   workup.ADDITIONwere added
4. 4
   OtherThe layers were separated
5. 5
   Extractionthe aqueous layer was extracted twice with methylene chloride
6. 6
   Washwashed with brine
7. 7
   Dryingdried over MgSO4
8. 8
   Concentrationconcentrated
9. 9
   Otherto yield 1.1 g crude product, which
10. 10
    Otherwas purified by recrystallization from hexane

Procedure

To a solution of 1.5 g (5.9 mmol) of 2-phenyl-6-trifluoromethyl-4(3H)-pyrimidinone, 17.2 g (226.3 mmol) dimethoxymethane, and 35 mL of chloroform was added 2.5 g (17.6 mmol) phosphorous pentoxide, at room temperature. By TLC (25% ethyl acetate in hexane) the reaction was incomplete after 4 h and an additional 3 g (21.1 mmol) phosphorous pentoxide was added. Stirring was continued for 16 h. The reaction mixture was poured onto crushed ice and 1M sodium hydroxide and methylene chloride were added. The layers were separated and the aqueous layer was extracted twice with methylene chloride. The organic extracts were combined and washed with brine, then dried over MgSO4 and concentrated to yield 1.1 g crude product, which was purified by recrystallization from hexane. Thus, 0.55 g (32%) 3-methoxymethyl-2-phenyl-6-trifluoromethyl-4(3H)-pyrimidinone (Compound 6) as a yellow solid was obtained. 1H-NMR (CDCl3) δ 3.55(3H,s); 5.2(2H,d); 6.85(1H,s); 7.65(3H,m); 7.75(2H,m).

Source