Toluene-4-sulfonic acid 2-(2-biphenyl-4-yl-methyl-oxazol-4-yl)ethyl ester → 3-{4-[2-(2-Biphenyl-4-yl-5-methyl-oxazol-4-yl)-ethoxy]-phenyl}-2-methyl-2-(4-tert-butylphenoxy)-propionic acid

Temperature

55 °C

Toluene-4-sulfonic acid 2-(2-biphenyl-4-yl-5-methyl-oxazol-4-yl)-ethyl ester (0.132 mmol) (see Ex. 1, Part I)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-(4-tert-butylphenoxy)-propionic 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 preparative thin-layer silica chromatography eluting with 93:7 CH2Cl2:methanol to produce a white solid (22%). MS [EI+] 590 (M+H)+, [EI−] 588 (M−H)+

1. addition1, Part I)was added to a one dram
2. customscrew-cap vial
3. customthe vial was tightly closed
4. filtrationThe suspension was filtered
5. temperaturewhile warm
6. washthe residue washed with ethanol (1 mL)
7. additionThe solution was treated with aqueous NaOH (5N solution, 100 μl)
8. temperatureThe solution was heated in a block heater at 55° C. for 3–16 h
9. customthe completion of the hydrolysis
10. customThe solvents are removed with a stream of nitrogen or under reduced pressure
11. dissolutionthe residue redissolved in 1 mL water
12. customprecipitation of product
13. additionThe suspension was diluted with dichloromethane (3 mL)
14. filtrationthe resultant biphasic solution was filtered through a Chrom-Elut column
15. customto remove water
16. concentrationThe filtrate was concentrated in vacuo
17. customthe resultant residue was purified by preparative thin-layer silica chromatography
18. washeluting with 93:7 CH2Cl2

ORD record

ord-d3737c080b5248ff86736f0776f91aa6

Source dataset

uspto-grants-2007_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07176224B2