반응 #45047

반응 방정식

Methyl 2-iodobenzoate

1-(3-Methylisoxazol-5-yl)methanamine

potassium phosphate

S-Phos

→

methyl 2-{[(3-methylisoxazol-5-yl)methyl]amino}-benzoate

수율 45.6%

용매

water

toluene

반응 조건

후처리

1. 1
   workup.WAITat 90° C. for 6 h
2. 2
   온도to cool
3. 3
   추출extracted with ethyl acetate (3×60 ml)
4. 4
   세척The combined extracts were washed with brine
5. 5
   건조dried over MgSO4
6. 6
   여과filtered
7. 7
   기타evaporated
8. 8
   기타The residual gummy oil was triturated with ether resulting in precipitation of a small amount of a yellow solid which
9. 9
   여과was filtered off
10. 10
    기타The filtrate was evaporated
11. 11
    기타triturated again with methanol
12. 12
    기타a second precipitate was removed by filtration
13. 13
    기타The filtrate was evaporated
14. 14
    기타purified by silica column chromatography
15. 15
    세척eluting with DCM
16. 16
    기타The product fractions were evaporated

실험 절차

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+)

출처