4-Phenoxybenzoic acid → {4-Methyl-5-[5-(4-phenoxyphenyl)-1,2,4-oxadiazol-3-yl]-2-thienyl}methanol

To a solution of 4-phenoxybenzoic acid (0.14 g, 0.63 mmol) in a mixture of acetonitrile (4 ml) and tetrahydrofuran (2 ml) were added successively 1-hydroxybenzotriazole (89 mg, 0.66 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.13 g, 0.66 mmol) and 5-({[t-butyl(dimethyl)silyl]oxy}methyl)-N′-hydroxy-3-methylthiophene-2-carboximidamide (0.18 g, 0.60 mmol) that was obtained in Example 11 (11d) with stirring, and the resulting mixture was stirred at 50° C. for 30 minutes. After stirring, water (5 ml) was added to the reaction mixture to quench the reaction, and the resulting mixture was extracted with ethyl acetate. The extract was washed successively with 0.1N hydrochloric acid, a saturated aqueous solution of sodium hydrogencarbonate and a saturated aqueous solution of sodium chloride and dried over sodium sulfate. After filtration, the filtrate was evaporated in vacuo. Subsequently, to a solution of the residue obtained in tetrahydrofuran (5 ml) was added a 1.0 M solution of tetrabutylammonium fluoride in tetrahydrofuran (1.2 ml, 1.2 mmol) with stirring, and the resulting mixture was stirred at 50° C. for 2 hours. After stirring, the reaction mixture was poured into water (20 ml) to quench the reaction and extracted with ether. The extract was washed with a saturated aqueous solution of sodium chloride and dried over sodium sulfate. After filtration, the filtrate was evaporated in vacuo, and the crude product of the title compound thus obtained was purified by chromatography on a silica gel column using a mixed solvent of ethyl acetate and hexane (1:3 to 1:2) as the eluent to afford the title compound (0.19 g) in a yield of 86% as a white crystalline solid.

1. stirringthe resulting mixture was stirred at 50° C. for 30 minutes
2. stirringAfter stirring
3. customto quench
4. customthe reaction
5. extractionthe resulting mixture was extracted with ethyl acetate
6. washThe extract was washed successively with 0.1N hydrochloric acid
7. dry with materiala saturated aqueous solution of sodium hydrogencarbonate and a saturated aqueous solution of sodium chloride and dried over sodium sulfate
8. filtrationAfter filtration
9. customthe filtrate was evaporated in vacuo
10. customSubsequently, to a solution of the residue obtained in tetrahydrofuran (5 ml)
11. stirringwith stirring
12. stirringthe resulting mixture was stirred at 50° C. for 2 hours
13. stirringAfter stirring
14. customto quench
15. customthe reaction
16. extractionextracted with ether
17. washThe extract was washed with a saturated aqueous solution of sodium chloride
18. dry with materialdried over sodium sulfate
19. filtrationAfter filtration
20. customthe filtrate was evaporated in vacuo

ORD record

ord-d2c2989ff822436fb2cf0e9923dfb335

Source dataset

uspto-grants-2010_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07687491B2