反应详情

1-(3-Methylisoxazol-5-yl)methanamine (155 mg, 1.37 mmol, 1.2 eq), potassium phosphate (341 mg, 1.60 mmol, 1.4 eq), S-Phos (95 mg, 0.230 mmol, 0.2 eq) and Pd2dba3 (13 mg, 0.06 mmol, 0.05 eq) were stirred in toluene (5 ml) under nitrogen. Methyl 2-iodobenzoate (300 mg, 1.14 mmol, 1 eq) was added and the mixture was stirred at room temperature for 3 days, then at 90° C. for 6 h. The reaction mixture was allowed to cool, poured into water (100 ml) and extracted with ethyl acetate (3×60 ml). The combined extracts were washed with brine, dried over MgSO4, filtered and evaporated. The residual gummy oil was triturated with ether resulting in precipitation of a small amount of a yellow solid which was filtered off. The filtrate was evaporated and triturated again with methanol and a second precipitate was removed by filtration. The filtrate was evaporated, then purified by silica column chromatography, eluting with DCM. The product fractions were evaporated to afford methyl 2-{[(3-methylisoxazol-5-yl)methyl]amino}-benzoate as a yellow oily gum (128 mg, 45% yield); 1H NMR (399.902 MHz, CDCl3) δ 2.25 (s, 3H), 3.88 (s, 3H), 4.53 (d, 2H), 5.99 (s, 1H), 6.62-6.70 (m, 2H), 7.32-7.38 (m, 1H), 7.92-7.96 (m, 1H), 8.19 (t, 1H). MS: m/z 247 (MH+)

1. waitat 90° C. for 6 h
2. temperatureto cool
3. extractionextracted with ethyl acetate (3×60 ml)
4. washThe combined extracts were washed with brine
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. customevaporated
8. customThe residual gummy oil was triturated with ether resulting in precipitation of a small amount of a yellow solid which
9. filtrationwas filtered off
10. customThe filtrate was evaporated
11. customtriturated again with methanol
12. customa second precipitate was removed by filtration
13. customThe filtrate was evaporated
14. custompurified by silica column chromatography
15. washeluting with DCM
16. customThe product fractions were evaporated