反应详情

To a solution of N-[3-(tert-Butyl-dimethyl-silanyloxy)-propoxy]-4-fluoro-2-(4-iodo-2-methyl-phenylamino)-benzamide (4.0 g, 7.27 mmol) in methanol (5 mL) at ambient temperature was added 5 M H2SO4 in methanol (0.073 mL, 0.364 mmol). After 1 h of stirring, to the reaction was added additional 5 M H2SO4 in methanol (0.035 mL, 0.182 mmol). After 2 h of stirring, the reaction was adjusted to pH 7 using saturated NaHCCO3 (aq) (c. a. 1.5 mL), followed by addition of water (35 mL). The aqueous layer was extracted with ethyl acetate (1×20 mL, 2×10 mL). The extracts were combined, washed with brine, and dried over magnesium sulfate. The resultant mixture was filtered, and the filtrate solvent was removed in vacuo to obtain an oil that was dried on a vacuum pump over the weekend. The oil was purified by flash chromatography, eluted with a gradient of 100% hexanes to 100% ethyl acetate in 50 min. The solvent was removed in vacuo of combined fractions to obtain a solid which was dried on a vacuum pump for c. a. 6 h. Recrystalized solid in a mixture of hexanes and ethyl acetate to afford 4-fluoro-N-(3-hydroxy-propoxy)-2-(4-iodo-2-methyl-phenylamino)-benzamide as a solid (2.4 g, 74% yield): m.p. 120.8-122.4 C.; 1H-NMR (400 MHz, (CD3)2CO) δ 10.91 (br s, 1H), 9.59 (br. S, 1H), 9.68 (m, 2H), 7.57 (d, 1H, J=8.54 Hz), 7.18 (d, 1H, J=8.34 Hz), 6.72 (m, 1H); 6.53 (m, 1H); 4.12 (t, 2H, J=6.11 Hz), 3.71 (t, 2H, J=5.86 Hz), 2.26 (s, 3H), 1.86 (m, 2H); 19F-NMR (376 MHz, (CD3)2CO) δ −108.14; MS 445.1 m/z (AP+), 443.1 m/z (AP−). Anal. Calcd. for C17H18FIN2O3: C, 45.96; H,L 4.08; N, 6.31; F, 4.28; I, 28.57. Found: C, 45.78; H, 3.88; N, 6.14; F, 4.30; I, 28.27.

1. stirringAfter 2 h of stirring
2. extractionThe aqueous layer was extracted with ethyl acetate (1×20 mL, 2×10 mL)
3. washwashed with brine
4. dry with materialdried over magnesium sulfate
5. filtrationThe resultant mixture was filtered
6. customthe filtrate solvent was removed in vacuo
7. customto obtain an oil that
8. customwas dried on a vacuum pump over the weekend
9. customThe oil was purified by flash chromatography
10. washeluted with a gradient of 100% hexanes to 100% ethyl acetate in 50 min
11. customThe solvent was removed in vacuo of combined fractions
12. customto obtain a solid which
13. customwas dried on a vacuum pump for c
14. custom6 h
15. customRecrystalized solid
16. additionin a mixture of hexanes and ethyl acetate