Hydrochloric Acid → HCID 69423034, compound

Methanesulfonyl chloride was added dropwise to a mixture of [3-isopropyl-1-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyl]-1H-pyrazol-4-yl]methanol (2.02 g), triethylamine (0.8 ml) and ethyl acetate (30 ml) at 0° C., which was stirred at room temperature for 3 hours. The reaction mixture was poured into water, which was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried (MgSO4), then concentrated. The residue was dissolved in tetrahydrofuran (20 ml). This solution was added dropwise at 0° C. to separately-prepared tetrahydrofuran solution (30 ml) of sodium diethyl malonate using diethyl malonate (2.35 g) and sodium hydride (60%, oily, 0.55 g). The reaction mixture was poured into dilute hydrochloric acid, which was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried (MgSO4), then concentrated. The residue was dissolved in ethanol (50 ml), then 1N aqueous sodium hydroxide solution (15 ml) was added to the solution, which was stirred at 60° C. for 2 hours. After the reaction solvent was removed under reduced pressure, water was added to the mixture, which was acidified with dilute hydrochloric acid. After the crystals obtained were filtered and washed with water, the crystals were dissolved in pyridine (50 ml), which was stirred at 120° C. for 2 hours. After pyridine was removed under reduced pressure, the residue was dissolved in ethyl acetate, which was washed with dilute hydrochloric acid, then with saturated aqueous sodium chloride solution, and dried (MgSO4), then concentrated. The crystals obtained were collected by filtration to yield 3-[3-isopropyl-1-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy) benzyl]-1H-pyrazol-4-yl]propionic acid (1.23 g, yield: 55%). This was recrystallized from ethyl acetate-hexane. Melting point: 97–98° C.

1. extractionwas extracted with ethyl acetate
2. washThe ethyl acetate layer was washed with saturated aqueous sodium chloride solution
3. dry with materialdried (MgSO4)
4. concentrationconcentrated
5. dissolutionThe residue was dissolved in tetrahydrofuran (20 ml)
6. additionThis solution was added dropwise at 0° C.
7. customto separately-prepared tetrahydrofuran solution (30 ml) of sodium diethyl malonate
8. extractionwas extracted with ethyl acetate
9. washThe ethyl acetate layer was washed with saturated aqueous sodium chloride solution
10. dry with materialdried (MgSO4)
11. concentrationconcentrated
12. dissolutionThe residue was dissolved in ethanol (50 ml)
13. addition1N aqueous sodium hydroxide solution (15 ml) was added to the solution, which
14. stirringwas stirred at 60° C. for 2 hours
15. customAfter the reaction solvent was removed under reduced pressure, water
16. additionwas added to the mixture, which
17. customAfter the crystals obtained
18. filtrationwere filtered
19. washwashed with water
20. dissolutionthe crystals were dissolved in pyridine (50 ml)
21. stirringwhich was stirred at 120° C. for 2 hours
22. customAfter pyridine was removed under reduced pressure
23. dissolutionthe residue was dissolved in ethyl acetate
24. washwhich was washed with dilute hydrochloric acid
25. dry with materialwith saturated aqueous sodium chloride solution, and dried (MgSO4)
26. concentrationconcentrated
27. customThe crystals obtained
28. filtrationwere collected by filtration

ORD record

ord-d38ac685de4d48229fa9f6b70922d727

Source dataset

uspto-grants-2007_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07179823B1