反应详情

A solution of 1.89 (10.6 mmol) of 1-(4-hydroxyphenyl)piperazine and 2.19 g (10 mmol) of 4-chloro-5,6-dimethyl-2-phenylpyrimidine in 30 ml of absolute N,N-dimethylformamide (DMF) was warmed to 80° C., and 234 mg of powdered K2CO3 were added at 80° C., with stirring, under a nitrogen atmosphere in each case after 10 minutes, after a further 25 minutes and after a further 60 minutes (total addition of 702 mg (5.08 mmol) of K2CO3). The mixture was stirred for a further 6 hours at 90° C., the DMF was substantially removed by distillation in an oil-pump vacuum in a rotary evaporator, the residue remaining was taken up in CH2Cl2 /water, and the pH was adjusted to 7-8 using dilute hydrochloric acid. After thoroughly mixing and separating the phases, the aqueous phase was extracted a further twice with CH2Cl2. The combined CH2Cl2 extracts were dried, filtered and evaporated in vacuo. The crystalline residue (3.6 g) was chromatographed on a silica gel S/CH2Cl2 column (diameter 2.0 cm, height 38 cm) by elution with CH2Cl2 and CH2Cl2 /C2H5OH mixtures with increasing C2H5OH content (to a maximum of 10% by volume of C2H5OH). The substance was drawn onto the column using 60 ml of a CH2Cl2 /tetra-hydrofuran 2:1 mixture. The eluted, not completely pure, crystalline substance was purified by boiling with a little CH2Cl2 and filtering off under suction. 2.22 g (=61.5% yield) of pure 1-(4-hydroxyphenyl)-4-(5,6-dimethyl-2-phenylpyrimidin-4-yl)piperazine, melting point 202°-03° C., were obtained;

1. stirringThe mixture was stirred for a further 6 hours at 90° C.
2. customthe DMF was substantially removed by distillation in an oil-pump vacuum in a rotary evaporator
3. additionAfter thoroughly mixing
4. customseparating the phases
5. extractionthe aqueous phase was extracted a further twice with CH2Cl2
6. dry with materialThe combined CH2Cl2 extracts were dried
7. filtrationfiltered
8. customevaporated in vacuo
9. customThe crystalline residue (3.6 g) was chromatographed on a silica gel S/CH2Cl2 column (diameter 2.0 cm, height 38 cm) by elution with CH2Cl2 and CH2Cl2 /C2H5OH
10. customThe eluted, not completely pure, crystalline substance was purified
11. filtrationfiltering off under suction