反应详情

温度

55 °C

The following example exemplifies the general procedure for the parallel synthesis of analogs utilizing the DynaVac carousel. To a 50 mL glass tube with screw cap and nitrogen inlet were charged 2-(2-butyl-5-hydroxyphenoxy)-2-methylpropionic acid ethyl ester, (0.050 g, 0.178 mmol), toluene-4-sulfonic acid 2-(5-methyl-2-bipheny-4-yl-loxazol-4-yl)ethyl ester (0.187 mmol) (see Ex. 1, part F), and powdered potassium carbonate (0.050 g, 0.36 mmol) in 1 mL of absolute ethanol. The mixture was heated to reflux for 18 h. MS analysis of the reaction indicated that 2-{5-[2-(2-biphenyl-4-yl-5-methyloxazol-4-yl)ethoxy]-2-butylphenoxy}-2-methylpropionic acid ethyl ester, MS (ES) m/e 542 (M+1) had formed. Next 0.4 mL of 5 N sodium hydoxide was added and the reaction was heated for 3 h at 55° C. The ethanol was removed in vacuo and the residue was treated with 1 mL of 5N hydrochloric acid and 1 mL of dichloromethane and poured into a 3 mL ChemElute column to remove the aqueous layer. The column was eluted with additional dichloromethane until nothing UV active remained on the column. The solvent was removed in vacuo. The crude residue was purified by mass-directed reverse phase HPLC to provide 2-{5-[2-(2-biphenyl-4-yl-5-methyloxazol-4-yl)ethoxy]-2-butylphenoxy}-2-methylpropionic acid. 1H NMR (400 MHz, CDCl3) δ 8.06 (d, J=8.3 Hz, 2H), 7.70 (d, J=8.3 Hz, 2H), 7.64 (d, J=8.3 Hz, 2H), 7.47 (t, J=7.6 Hz, 2H), 7.39 (t, J=7.3 Hz, 1H), 7.04 (d, J=8.3 Hz, 1H), 6.69 (d, J=2.4 Hz, 1H), 6.53 (dd, J=8.3, 2.4 Hz, 1H), 4.20 (t, J=7.6 Hz, 2H), 2.94 (t, J=7.6 Hz, 2H), 2.55 (t, J=7.8 Hz, 2H), 2.38 (s, 3H), 1.64 (s, 6H), 1.55 (quintet, J=7.7 Hz, 2H), 1.35 (sextet, J=7.5 Hz, 2H), 0.93 (t, J=7.3 Hz, 3H), MS (ES) m/e 514 (M+1).

1. customfor the parallel synthesis of analogs
2. customTo a 50 mL glass tube with screw cap
3. temperatureThe mixture was heated
4. temperatureto reflux for 18 h
5. customMS (ES) m/e 542 (M+1) had formed
6. customThe ethanol was removed in vacuo
7. additionthe residue was treated with 1 mL of 5N hydrochloric acid and 1 mL of dichloromethane
8. additionpoured into a 3 mL ChemElute column
9. customto remove the aqueous layer
10. washThe column was eluted with additional dichloromethane until nothing UV
11. customThe solvent was removed in vacuo
12. customThe crude residue was purified by mass-directed reverse phase HPLC