反应详情

In a 50 ml flame-dried round bottom flask, a suspension of zinc (0.183 g, 0.00280 mol), chlorotrimethylsilane (8.9 uL, 0.000070 mol) and 1,2-dibromoethane (6.0 uL, 0.000070 mol) in N,N-dimethylformamide (2.4 mL, 0.031 mol) was stirred for 15 minutes. To this was added a solution of 3-fluoro-4-chlorobenzylbromide (0.626 g, 0.00280 mol) in N,N-dimethylformamide (4.8 mL, 0.062 mol), and the resulting suspension was stirred overnight at room temperature. To a flame-dried 50 ml round bottom flask containing ethyl 4-bromo-2-morpholin-4-yl-1,3-thiazole-5-carboxylate (0.300 g, 0.000934 mol) and bis(tri-t-butylphosphine)palladium(0) (36 mg, 0.000070 mol) was added the organozinc solution from above, and the reaction was heated with stirring at 60° C. for 60 min. Reaction was quenched with saturated ammonium chloride, and then transferred to a separatory funnel containing water (10 mL) and EtOAc (40 mL). The layers were separated, and the aqueous layer was extracted 2×30 mL with EtOAc. The combined organic layers were washed 1× brine, dried over Na2SO4, filtered, and concentrated in vacuo. The resulting residue was dissolved in DCM, adsorbed onto silica gel and purified via column chromotography (24 gram Isco column, gradient elution, 0-50% EtOAc/hexanes) to afford ethyl 4-(4-chloro-3-fluorobenzyl)-2-morpholin-4-yl-1,3-thiazole-5-carboxylate (245 mg, yield 68.2%).

1. customIn a 50 ml flame-dried round bottom flask
2. stirringthe resulting suspension was stirred overnight at room temperature
3. temperaturewas heated
4. stirringwith stirring at 60° C. for 60 min
5. customReaction
6. customwas quenched with saturated ammonium chloride
7. customtransferred to a separatory funnel
8. additioncontaining water (10 mL) and EtOAc (40 mL)
9. customThe layers were separated
10. extractionthe aqueous layer was extracted 2×30 mL with EtOAc
11. washThe combined organic layers were washed 1× brine
12. dry with materialdried over Na2SO4
13. filtrationfiltered
14. concentrationconcentrated in vacuo
15. dissolutionThe resulting residue was dissolved in DCM
16. custompurified via column chromotography (24 gram Isco column, gradient elution, 0-50% EtOAc/hexanes)