Methanol → (6-(Pyridin-2-yloxymethyl)-pyridin-3-yl)-acetohydroximoyl chloride

To a methanol (5 mL) solution of 5-(2-nitro-ethyl)-2-(pyridin-2-yloxymethyl)-pyridine (93 mg, 0.36 mmol) described in Manufacturing Example 154-1-7 was added lithium methoxide (27 mg, 0.72 mmol), which was stirred for 5 minutes at room temperature. The reaction mixture was concentrated under a reduced pressure. To a suspension of this residue in tetrahydrofuran (3 mL) and methylene chloride (3 mL) was added titanium (IV) tetrachloride (87 μL, 0.79 mmol) under nitrogen atmosphere at −78° C., which was stirred for 2 hours at 0° C. More titanium(IV) tetrachloride (50 μL, 0.46 mmol) was added at −78° C., which was stirred for 3 hours at 0° C. Water was added to the reaction mixture at 0° C., which was then extracted with ethyl acetate. The organic layer was separated, washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and then filtered. The filtrate was concentrated under a reduced pressure to obtain the title compound (24 mg). This compound was used in the following reaction without any further purification.

1. concentrationThe reaction mixture was concentrated under a reduced pressure
2. additionTo a suspension of this residue in tetrahydrofuran (3 mL)
3. stirringwhich was stirred for 2 hours at 0° C
4. stirringwhich was stirred for 3 hours at 0° C
5. extractionwhich was then extracted with ethyl acetate
6. customThe organic layer was separated
7. washwashed with saturated aqueous sodium chloride
8. dry with materialdried over anhydrous magnesium sulfate
9. filtrationfiltered
10. concentrationThe filtrate was concentrated under a reduced pressure

ORD record

ord-b2d95892b022476aa85fa924977167b5

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08841327B2