反应详情

To a solution of methyl propionate (0.088 mL, 0.89 mmol) and 6-bromo-2-chlorobenzo[d]thiazole (221 mg, 0.89 mmol) in degassed toluene (5 mL) at brine/ice bath temperature was slowly added 1.0 M NaHMDS in THF (2.22 mL, 2.22 mmol). After the addition was complete, the reaction was stirred for 10 min. The mixture was then quenched with satd. NH4Cl (15 mL) then extracted with EtOAc (2×20 mL). The organic extracts were dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography eluting with 0-100% EtOAc/hexane to give Compound R3a (198 mg, 0.66 mmol, 74% yield) as a yellow solid. LCMS=1.0 min using analytical method (M), 302.0 (M+H). 1H NMR (400 MHz, CDCl3) δ 8.02 (d, J=1.8 Hz, 1H), 7.87 (d, J=8.8 Hz, 1H), 7.58 (dd, J=8.7, 1.9 Hz, 1H), 4.30 (q, J=7.3 Hz, 1H), 3.78 (s, 3H), 1.75 (d, J=7.3 Hz, 3H).

1. additionAfter the addition
2. customThe mixture was then quenched with satd
3. extractionNH4Cl (15 mL) then extracted with EtOAc (2×20 mL)
4. dry with materialThe organic extracts were dried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe residue was purified by silica gel chromatography
8. washeluting with 0-100% EtOAc/hexane
9. customto give Compound R3a (198 mg, 0.66 mmol, 74% yield) as a yellow solid
10. customLCMS=1.0 min