Methanol → (6-(2-Fluoro-phenoxy)-pyridin-3-yl)-acetohydroximoyl chloride

To a mixture of 2-(2-fluoro-phenoxy)-5-(2-nitro-ethyl)-pyridine (150 mg, 0.59 mmol) described in Manufacturing Example 74-1-3 and methanol (1.5 mL) was added lithium methoxide (45 mg, 1.2 mmol) at room temperature, which was stirred for 5 minutes at room temperature. The solvent was evaporated from the reaction mixture under a reduced pressure. Titanium (IV) chloride (140 μL, 1.3 mmol) was added at −78° C. to a mixture of the resulting residue, methylene chloride (2 mL) and tetrahydrofuran (1 mL), and stirred for 80 minutes at 0° C. The reaction mixture was cooled to −78° C., water (1 mL) was added, and the temperature was gradually raised to room temperature. Water was added to the reaction solution at room temperature, which was then extracted with ethyl acetate. The organic layer was washed with water until the pH was 5, and then washed with saturated aqueous sodium chloride. The organic layer was dried over anhydrous magnesium sulfate, and was concentrated under a reduced pressure to obtain the title compound (160 mg) as a crude product. This compound was used in the subsequent reaction without further purification.

1. customThe solvent was evaporated from the reaction mixture under a reduced pressure
2. stirringstirred for 80 minutes at 0° C
3. temperatureThe reaction mixture was cooled to −78° C.
4. temperaturethe temperature was gradually raised to room temperature
5. extractionwhich was then extracted with ethyl acetate
6. washThe organic layer was washed with water until the pH was 5
7. washwashed with saturated aqueous sodium chloride
8. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
9. concentrationwas concentrated under a reduced pressure

ORD record

ord-40b42c812e3d4e398af81ff6849b5a8e

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08507530B2