Ethyl chloroformate → 4-{[4-({[4-(4,5-dihydro-1,3-oxazol-2-ylmethyl)-1-phenyl-1H-pyrazol-3-yl]oxy}methyl)-2-methoxyphenoxy]methyl}-2-(2-furyl)-5-methyl-1,3-oxazole

To a mixture of {3-[(4-{[2-(2-furyl)-5-methyl-1,3-oxazol-4-yl]methoxy}-3-methoxybenzyl)oxy]-1-phenyl-1H-pyrazol-4-yl}acetic acid (0.70 g), triethylamine (0.17 g) and tetrahydrofuran (30 mL) was added ethyl chlorocarbonate (0.18 g) at −30° C., and the mixture was stirred at the same temperature for 40 min. The reaction mixture was added to a mixture of 1-amino-2-chloroethane hydrochloride (0.81 g), triethylamine (0.71 g) and tetrahydrofuran (20 mL) at −30° C., and the mixture was stirred at room temperature for 1 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. A mixture of the obtained residue, potassium carbonate (0.24 g) and N,N-dimethylformamide (20 mL) was stirred at 90° C. for 2 hrs. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography to give 4-{[4-({[4-(4,5-dihydro-1,3-oxazol-2-ylmethyl)-1-phenyl-1H-pyrazol-3-yl]oxy}methyl)-2-methoxyphenoxy]methyl}-2-(2-furyl)-5-methyl-1,3-oxazole as colorless crystals (0.14 g, yield 18%) from a fraction eluted with ethyl acetate-methanol (50:1, v/v). Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 95-96° C.

1. stirringthe mixture was stirred at room temperature for 1 hr
2. extractionthe mixture was extracted with ethyl acetate
3. washThe organic layer was washed with saturated brine
4. dry with materialdried over anhydrous magnesium sulfate
5. concentrationconcentrated
6. additionA mixture of the obtained residue, potassium carbonate (0.24 g) and N,N-dimethylformamide (20 mL)
7. stirringwas stirred at 90° C. for 2 hrs
8. additionWater was poured into the reaction mixture
9. extractionthe mixture was extracted with ethyl acetate
10. washThe organic layer was washed with saturated brine
11. dry with materialdried over anhydrous magnesium sulfate
12. concentrationconcentrated

ORD record

ord-69248c1ba91d489aa8e34aa7a06b0320

Source dataset

uspto-grants-2008_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07368578B2