2-Phenoxy-3-(naphthalen-1-yl)-2-methylpropionic acid ethyl ester → 3-{4-[2-(2-Biphenyl-3-yl-5-methyl-oxazol-4-yl)-ethoxy]-naphthalen-1-yl}-2-methyl-2-phenoxypropionic acid

Temperature

55 °C

Toluene-4-sulfonic acid 2-(5-methyl-2-(4-thiophen-2-yl-phenyl)-oxazol-4-yl)-ethyl ester (0.132 mmol) (see Ex. 3, Part B) was added to a one dram, screw-cap vial and diluted with ethanol (0.5 mL). To this solution are added 2-phenoxy-3-(naphthalen-1-yl)-2-methylpropionic acid ethyl ester (see Ex. 12, Part B) (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, 100·1) 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 hew 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, 150·1), 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 produce a white solid (7%). MS [EI+] 590 (M+H)+, [EI−] 588 (M−H)+

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, 100·1)
7. temperatureThe solution was heated in a block heater at 55° C. for 3–16 h
8. customthe completion of hew 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

ORD record

ord-79812f4e52b0402bb7b356d16cb11448

Source dataset

uspto-grants-2007_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07176224B2