反应详情

The 7-methoxy-8-methyl-2-(4-(trifluoromethyl)thiazol-2-yl)quinolin-4-ol BO (10.0 g, 1 eq.), the N-Boc-trans-4-hydroxyproline methyl ester BP (7.20 g, 1 eq.), and the triphenylphosphine (11.56 g, 1.5 eq.) in suspension in THF (250 mL) under N2 were cooled down to 0° C. The DIAD (8.70 mL, 1.5 eq.) was added dropwise. The reaction mixture was allowed to warm up and stir at room temperature for 1.25 hrs, then cooled again at 0° C. and additional 1 more eq. of DIAD was added. The reaction mixture was stirred for 2 hrs at room temperature, and then concentrated in vacuo to 50 mL. Water and ethyl acetate were added and the phases were separated. The aqueous layer was further extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel to yield compound BQ (16.75 g, 87% purity). MS (ESI, EI+) m/z=568.3 (MH+); 626.5 (M+OAc−).

1. temperatureto warm up
2. temperaturecooled again at 0° C.
3. stirringThe reaction mixture was stirred for 2 hrs at room temperature
4. concentrationconcentrated in vacuo to 50 mL
5. additionWater and ethyl acetate were added
6. customthe phases were separated
7. extractionThe aqueous layer was further extracted with ethyl acetate
8. washThe organic layer was washed with brine
9. dry with materialdried over magnesium sulfate
10. concentrationconcentrated under reduced pressure
11. customThe residue was purified by chromatography on silica gel
12. customto yield compound BQ (16.75 g, 87% purity)