Toluene → 5-(Chloromethyl)-2-methoxypyridine

To a solution of (6-methoxypyridin-3-yl)methanol (2) (537.8 g, 3.86 mol) obtained in Preparation Example 1 in dimethylformamide (1.6 L) was added dropwise thionyl chloride (310 mL, 4.25 mol) over a period of 1.3 hours while cooling in an ice bath under a nitrogen atmosphere. After stirring for 1 hour while cooling in an ice bath, toluene (5.4 L) and a 2N aqueous solution of sodium hydroxide (5.4 L) were added successively to the reaction mixture at 23° C. or below. The reaction mixture was stirred for about 10 minutes and then the aqueous layer was separated, the organic layer was washed with water (2.7 L). The organic layer was concentrated under reduced pressure to dryness, and then toluene (1.0 L) was added to the residue and azeotropic distillation was carried out to give 618.8 g of the title compound as a pale yellow oil (content 556.3 g, yield 91.4%).

1. temperaturewhile cooling in an ice bath under a nitrogen atmosphere
2. temperaturewhile cooling in an ice bath
3. stirringThe reaction mixture was stirred for about 10 minutes
4. customthe aqueous layer was separated
5. washthe organic layer was washed with water (2.7 L)
6. concentrationThe organic layer was concentrated under reduced pressure to dryness
7. additiontoluene (1.0 L) was added to the residue and azeotropic distillation

ORD record

ord-b436d440e96d4b559b6a6dca709a8122

Source dataset

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07538117B2