Sodium Hydroxide → HCID 178488125, compound

Temperature

17.5 °C

2-hydroxymethyl-3,5-dimethyl-4-methoxy pyridine hydrochloride (300 g) was charged to dichloromethane (1770 ml) and cooled to 15-20° C. Thionyl chloride (240 g) was added slowly at 15 to 20° C. and the contents were stirred at 25 to 30° C. for 1 hour. After reaction completion, water (300 ml) was added at 15 to 20° C. and allowed to attain 25 to 30° C. To this reaction mass 2-mercapto-5-methoxy benzimidazole (252 g) and tetrabutyl ammonium bromide (6 g) was added, and the pH of the reaction mass was adjusted to 10.0 to 10.5 at 5 to 15° C. using 30% sodium hydroxide solution and stirred for 2 hours at 15 to 20° C. maintaining pH 10.0-10.5. After reaction completion the dichloromethane layer was separated and the aqueous layer was extracted with dichloromethane (370 ml×2). The dichloromethane layer was then washed with water until the pH of the aqueous layer was 7.0 to 7.5, dried over sodium sulphate and partially concentrated at temperature below 50° C. under vacuum. Ethyl acetate (240 ml) was added and stripped off to remove traces of dichloromethane, further ethyl acetate (800 ml) was added and heated to 50 to 60° C., cooled to room temperature, chilled to 10 to −5° C. and maintained for 1 hour. The product was then filtered, washed with chilled ethyl acetate (200 ml). The product was then dried at 30 to 35° C. to yield 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)-methyl)thio]-1H benzimidazole form II (392 g, 80.6% yield).

1. additionwas added at 15 to 20° C.
2. customto attain 25 to 30° C
3. customwas adjusted to 10.0 to 10.5 at 5 to 15° C.
4. stirringstirred for 2 hours at 15 to 20° C.
5. temperaturemaintaining pH 10.0-10.5
6. customwas separated
7. extractionthe aqueous layer was extracted with dichloromethane (370 ml×2)
8. washThe dichloromethane layer was then washed with water until the pH of the aqueous layer
9. dry with materialdried over sodium sulphate
10. concentrationpartially concentrated at temperature below 50° C. under vacuum
11. additionEthyl acetate (240 ml) was added
12. customto remove traces of dichloromethane, further ethyl acetate (800 ml)
13. additionwas added
14. temperatureheated to 50 to 60° C.
15. temperaturecooled to room temperature
16. temperaturechilled to 10 to −5° C.
17. temperaturemaintained for 1 hour
18. filtrationThe product was then filtered
19. washwashed with chilled ethyl acetate (200 ml)
20. customThe product was then dried at 30 to 35° C.

ORD record

ord-e4c5069e659d4d00895345092b6fee18

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08394963B2