反应详情

温度

140 °C

Following the method described for in Example 21, compound 2-amino-N-(4-tert-butylphenyl)benzamide was made from 4-tert-butylaniline, in 99% yield, and was isolated as a brown solid. 2-Amino-N-(4-tert-butylphenyl)benzamide (1.14 g, 4.25 mmol) and 4-(2-(tert-butyldimethylsilyloxy)ethoxy)-3,5-dimethylbenzaldehyde (1.31 g, 4.25 mmol) were combined in DMA (20 mL) and p-TsOH (0.164 g, 0.86 mmol) was added, followed by NaHSO3 (0.488 g, 4.69 mmol). The mixture was heated to 140° C. for 24 hours, before concentrating, diluting with ethyl acetate (250 mL), washing with water (200 mL), and then brine (200 mL), before drying over Na2SO4, filtering, and concentrating. Purification by flash chromatography on silica gel, eluting with 1:1 ethyl acetate/hexanes to 100% ethyl acetate to 10% methanol/ethyl acetate, afforded the title compound as a white solid. 1H-NMR (300 MHz, DMSO-d6) δ 8.19 (d, J=7.2 Hz, 1H), 7.87-7.92 (m, 1H), 7.75 (d, J=8.0 Hz, 1H), 7.56-7.61 (m, 1H), 7.35 (d, J=8.5 Hz, 2H), 7.18 (d, J=8.5 Hz, 2H), 6.96 (s, 2H), 4.83 (t, J=5.4 Hz, 1H), 3.62-3.67 (m, 4H), 2.06 (s, 6H), 1.25 (s, 9H). MS (APCI) m/z: 443 (M+H)+.

1. customwas isolated as a brown solid
2. concentrationbefore concentrating
3. additiondiluting with ethyl acetate (250 mL)
4. washwashing with water (200 mL)
5. dry with materialbrine (200 mL), before drying over Na2SO4
6. filtrationfiltering
7. concentrationconcentrating
8. customPurification by flash chromatography on silica gel
9. washeluting with 1:1 ethyl acetate/hexanes to 100% ethyl acetate to 10% methanol/ethyl acetate