Methanol → (4-(3-Fluoro-pyridin-2-yloxymethyl)-phenyl)acetohydroximoyl chloride

To a methanol (10 mL) solution of 3-fluoro-2-(4-(2-nitro-ethyl)-benzyloxy)-pyridine (674 mg, 2.44 mmol) described in Manufacturing Example 149-1-3 was added lithium methoxide (185 mg, 4.87 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 (10 mL) and methylene chloride (10 mL) was added titanium (IV) tetrachloride (590 μL, 5.37 mmol) under nitrogen atmosphere at −78° C., which was stirred for 1 hour 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 with neutral silica gel. The filtrate was concentrated under a reduced pressure to obtain the title compound (629 mg, 88%). 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 (10 mL)
3. stirringwhich was stirred for 1 hour at 0° C
4. extractionwhich was then extracted with ethyl acetate
5. customThe organic layer was separated
6. washwashed with saturated aqueous sodium chloride
7. dry with materialdried over anhydrous magnesium sulfate
8. filtrationfiltered with neutral silica gel
9. concentrationThe filtrate was concentrated under a reduced pressure

ORD record

ord-c279308ab11d4ff39f2b6ea35b72aaab

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08841327B2