Sodium hydride → 4-[2-(3-Methyl-[1,2,4]oxadiazol-5-yl)-vinyl]-benzene-1,2-diol

A solution of N-hydroxy-acetamidine (0.17 g, 2.29 mmol) in dry tetrahydrofuran (5 mL) was added slowly into the suspension of 60% sodium hydride (0.14 g, 3.5 mmol) in dry tetrahydrofuran (5 mL) under nitrogen atmosphere at 0° C. to 10° C. The reaction mixture was stirred for 30 min at room temperature. 3-[3,4-Bis-(tert-butyl-dimethyl-silanyloxy)-phenyl]-acrylic acid methyl ester (compound of Example 1, Step 1; 0.5 g, 1.18 mmol) in dry tetrahydrofuran (5 mL) was added into the reaction mixture and heated at 60° C. for 8 h. The reaction mixture was cooled at 0° C. and quenched with MeOH (2 mL) to destroy excess sodium hydride. The reaction mixture was extracted with ethyl acetate (2×10 mL) and the combined organic layers were washed with water (2×10 mL) followed by brine (10 mL). The organic phase obtained was dried over anhydrous sodium sulphate and concentrated to dryness. The crude product obtained was purified by column chromatography (silica gel, chloroform-methanol) to afford the title compound.

1. temperatureheated at 60° C. for 8 h
2. temperatureThe reaction mixture was cooled at 0° C.
3. customquenched with MeOH (2 mL)
4. customto destroy excess sodium hydride
5. extractionThe reaction mixture was extracted with ethyl acetate (2×10 mL)
6. washthe combined organic layers were washed with water (2×10 mL)
7. customThe organic phase obtained
8. dry with materialwas dried over anhydrous sodium sulphate
9. concentrationconcentrated to dryness
10. customThe crude product obtained
11. customwas purified by column chromatography (silica gel, chloroform-methanol)

ORD record

ord-9b72aab94dfb42e4810576cb5f435157

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08629277B2