Triethylamine → (2Z)-2-[3-[4-[(5-methyl-2-phenyl-1,3-oxazol-4-yl)methoxy]phenyl]propoxyimino]-2-phenylacetic acid

To a solution of 3-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)phenyl]propanol (1.00 g) and triethylamine (0.866 ml) in ethyl acetate (30 ml), methanesulfonyl chloride (0.478 ml) was added dropwise at 0° C., and the mixture was stirred for 1 hour. The reaction mixture was washed with saturated aqueous sodium chloride, dried (MgSO4), and then concentrated. The residue was dissolved in N,N-dimethylformamide (10 ml), and methyl Z-2-hydroxyimino-2-phenylacetate (830 mg) and sodium hydride (60%, in oil, 185 mg) were added, and the mixture was stirred for 2 hours at room temperature. After adding 1N HCl (7 ml) and then aqueous sodium bicarbonate, the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride, dried (MgSO4) and then concentrated. The residue was subjected to column chromatography on silica gel to obtain a colorless oil from a fraction eluted with ethyl acetate-hexane-toluene (1:5:5, v/v). This oil was dissolved in tetrahydrofuran (10 ml)-methanol (5 ml), and 1N aqueous solution of sodium hydroxide (5 ml) was added, and then the mixture was stirred for 2 hour at 40° C. After adding 1N HCl (5.5 ml) to the reaction mixture, the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride, dried (MgSO4) and then concentrated. The residual crystal was recrystallized from ethyl acetate-hexane to obtain Z-2-[3-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)phenyl]propoxyimino]-2-phenylacetic acid (1.13 g, yield 78%) as colorless crystals. m.p. 165-166° C. (decomposition)

1. washThe reaction mixture was washed with saturated aqueous sodium chloride
2. dry with materialdried (MgSO4)
3. concentrationconcentrated
4. dissolutionThe residue was dissolved in N,N-dimethylformamide (10 ml)
5. additionmethyl Z-2-hydroxyimino-2-phenylacetate (830 mg) and sodium hydride (60%, in oil, 185 mg) were added
6. stirringthe mixture was stirred for 2 hours at room temperature
7. additionAfter adding 1N HCl (7 ml)
8. extractionaqueous sodium bicarbonate, the mixture was extracted with ethyl acetate
9. washThe ethyl acetate layer was washed with saturated aqueous sodium chloride
10. dry with materialdried (MgSO4)
11. concentrationconcentrated
12. customto obtain a colorless oil from a fraction
13. washeluted with ethyl acetate-hexane-toluene (1:5:5
14. dissolutionThis oil was dissolved in tetrahydrofuran (10 ml)-methanol (5 ml), and 1N aqueous solution of sodium hydroxide (5 ml)
15. additionwas added
16. stirringthe mixture was stirred for 2 hour at 40° C
17. additionAfter adding 1N HCl (5.5 ml) to the reaction mixture
18. extractionthe mixture was extracted with ethyl acetate
19. washThe ethyl acetate layer was washed with saturated aqueous sodium chloride
20. dry with materialdried (MgSO4)
21. concentrationconcentrated
22. customThe residual crystal was recrystallized from ethyl acetate-hexane

ORD record

ord-7e2faf3c2c774f8c9fe7c663f071ea9f

Source dataset

uspto-grants-2002_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06495581B1