反应详情

温度

55 °C

Standard Procedure (A): Toluene-4-sulfonic acid 2-(2-phenyl-5-methyl-oxazol-4-yl)-ethyl ester (0.47 g, 0.132 mmol) was added to a one dram, screw-cap vial and diluted with ethanol (0.5 mL). To this solution are added 3-(4-hydroxyphenyl)-2-methyl-2-phenoxypropionic acid ethyl ester (0.5 mL of a 0.264 M solution in ethanol, 0.132 mmol) and polystyrene bound 1,5,7-triazabicyclo[4.4.0]dec-5-ene (100-125 mg, 2.6 mmol/g) and the vial was tightly closed. The reaction vessel was heated in a block heater for 24-48 h at 55° C., or until TLC or MS analysis indicates the disappearance of starting materials. The suspension was filtered while warm and the residue washed with ethanol (1 mL). The solution was treated with aqueous NaOH (5N solution, 100 μl) and the vial resealed tightly. The solution was heated in a block heater at 55° C. for 3-16 h, or until MS analysis indicates the completion of the hydrolysis. The solvents are removed with a stream of nitrogen or under reduced pressure and the residue redissolved in 1 mL water. The solution was acidified with aqueous HCl (5N solution, 150 μl), often causing precipitation of product. The suspension was diluted with dichloromethane (3 mL) and the resultant biphasic solution was filtered through a Chrom-Elut column to remove water. The filtrate was concentrated in vacuo and the resultant residue was purified by mass-directed HPLC to provide analytically pure material. Overall yield after purification 25%. Standard Procedure (B): A mixture of 3-(4-hydroxy-phenyl)-2-methyl-2-m-tolyloxy-propionic acid ethyl ester (0.095 g, 0.030 mmol), toluene-4-sulfonic acid 2-(5-methyl-2-phenyl-oxazol-4-yl)-ethyl ester (0.108 g, 0.030 mmol) and 325 mesh K2CO3 (0.084 g, 0.60 mmol) in ethanol (2 mL) was heated to reflux for 24 h under N2. Aqueous 5N NaOH (0.5 mL) and additional ethanol (1 mL) was added to the reaction mixture and it was heated at reflux for an additional 2 h. The reaction was cooled and the solvent removed in vacuo. The residue was acidified with aqueous 1 N HCl (5 mL), extracted with water and CH2Cl2 and the organic layer dried by passing it through a Varian Chem Elut 1003 cartridge. The solvent was removed in vacuo to give 0.134 g of crude product which was purified by LCMS to give 0.036 g (25%) of analytically pure 2-methyl-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-phenyl}-2-m-tolyloxy-propionic acid.

1. customscrew-cap vial
2. customthe vial was tightly closed
3. filtrationThe suspension was filtered
4. temperaturewhile warm
5. washthe residue washed with ethanol (1 mL)
6. additionThe solution was treated with aqueous NaOH (5N solution, 100 μl)
7. temperatureThe solution was heated in a block heater at 55° C. for 3-16 h
8. customthe completion of the hydrolysis
9. customThe solvents are removed with a stream of nitrogen or under reduced pressure
10. dissolutionthe residue redissolved in 1 mL water
11. customprecipitation of product
12. additionThe suspension was diluted with dichloromethane (3 mL)
13. filtrationthe resultant biphasic solution was filtered through a Chrom-Elut column
14. customto remove water
15. concentrationThe filtrate was concentrated in vacuo
16. customthe resultant residue was purified by mass-directed HPLC
17. customto provide analytically pure material
18. customOverall yield
19. customafter purification 25%
20. temperaturewas heated
21. temperatureto reflux for 24 h under N2
22. temperaturewas heated
23. temperatureat reflux for an additional 2 h
24. temperatureThe reaction was cooled
25. customthe solvent removed in vacuo
26. extractionextracted with water and CH2Cl2
27. customthe organic layer dried
28. customThe solvent was removed in vacuo
29. customto give 0.134 g of crude product which
30. customwas purified by LCMS