反应详情

A mixture of 3-(4-chlorophenyl)-5-(piperazin-1-yl)-1,2,4-thiadiazole (100 mg, 356 μmol), 4-methoxyphenylacetophenone (64.3 mg, 392 μmol) and titanium IV propoxide (152 mg, 158 μl, 534 μmol) in 2 mL THF was stirred for 3 h at RT. NaBH4 (40.4 mg, 1.07 mmol) was added in three portions. MeOH (0.2 mL) was added and stirred over the weekend at RT. Water (5 mL), EtOAc (10 mL) and aq. 2N NaOH (3 mL) was added, stirred for 10 min and filtered over a dicalit-plug. The aqueous layer was separated and extracted once with EtOAc (20 mL). The organic layers were washed with brine (1×20 mL), dried over Na2SO4, filtered off and concentrated in vacuo. The residue was purified by column chromatography on silica eluting with a gradient formed from heptane and EtOAc and again with preparative HPLC to yield, after evaporation of the product containing fraction, 39 mg (25%) of the title compound as off-white solid. MS (m/e): 429.2 (MH+).

1. stirringstirred over the weekend at RT
2. stirringstirred for 10 min
3. filtrationfiltered over a dicalit-plug
4. customThe aqueous layer was separated
5. extractionextracted once with EtOAc (20 mL)
6. washThe organic layers were washed with brine (1×20 mL)
7. dry with materialdried over Na2SO4
8. filtrationfiltered off
9. concentrationconcentrated in vacuo
10. customThe residue was purified by column chromatography on silica eluting with a gradient
11. customformed from heptane and EtOAc and again with preparative HPLC
12. customto yield
13. customafter evaporation of the product
14. additioncontaining fraction, 39 mg (25%) of the title compound as off-white solid