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-9abcae9e645b4c869be97d6bc77507d6

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08507530B2