反应详情

温度

80 °C

In a 50 mL round bottom flask were combined ethyl 4-(4-chloro-3-fluorobenzyl)-2-morpholin-4-yl-1,3-thiazole-5-carboxylate (0.245 g, 0.000637 mol), tetrahydrofuran (5.49 mL, 0.0677 mol) and a solution of lithium hydroxide (2.0 M in water, 3.18 mL, 0.00637 mol). The mixture was heated at 80° C. with stirring for 2 days, and then cooled to room temperature and diluted with water. Reaction mixture was then carefully adjusted to pH 5 via addition of 1N HCl and transferred to a separatory funnel containing EtOAc (40 mL). 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 to afford a white solid, which was dissolved in DCM and adsorbed onto silica gel. Column chromatography (4 g column, gradient elution 0-20% MeOH in DCM) then afforded 4-(4-chloro-3-fluorobenzyl)-2-morpholin-4-yl-1,3-thiazole-5-carboxylic acid (118) (31 mg, 14%). LC/MS: (FA) ES+ 357, 359; NMR (400 MHz, DMSO) δ 12.79 (s, 1H), 7.48 (t, 0.1=8.1, 1H), 7.24 (dd, J=1.9, 10.5, 1H), 7.08 (dd, J=1.5, 8.3, 1H), 4.24 (s, 2H), 3.71-3.62 (m, 4H), 3.46-3.38 (m, 4H).

1. customIn a 50 mL round bottom flask were combined
2. temperaturecooled to room temperature
3. customReaction mixture
4. customtransferred to a separatory funnel
5. customLayers were separated
6. extractionthe aqueous layer was extracted 2×30 mL with EtOAc
7. washThe combined organic layers were washed 1× brine
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customto afford a white solid, which
12. washColumn chromatography (4 g column, gradient elution 0-20% MeOH in DCM)