Sodium Cyanide → (5-Chloro-2-methoxyphenyl)acetonitrile

To a solution of methyl 5-chloro-2-methoxybenzoate (25.4 g, 127 mmol) in ether (200 ml), cooled in an ice water bath, was added dropwise lithium tetrahydroaluminate (1 M in diethyl ether, 110 ml, 110 mmol). After 2 hours the reaction was quenched with water and then acidified to pH 3 with hydrochloric acid (6 M aqueous solution). The layers were separated and the organic layer dried over magnesium sulfate, filtered and concentrated in vacuo to give a white solid. The solid was dissolved dichloromethane (200 ml) and treated with thionyl chloride (25 ml, 340 mmol). After heating at reflux for 2 hours, the reaction was cooled to room temperature and water added. The layers were separated and the aqueous layer extracted with dichloromethane (2×50 ml). The combined organics were dried over magnesium sulfate, filtered and concentrated in vacuo to give an orange solid. This solid was dissolved dimethyl sulphoxide (175 ml), sodium cyanide (12.75 g, 260.2 mmol) added and solution heated to 80° C. for 3 hours. After cooling to room temperature, water was added and a solid formed that was filtered and washed with water to provide the title compound as an off white solid, 20.8 g, 91% yield.

1. customAfter 2 hours the reaction was quenched with water
2. customThe layers were separated
3. dry with materialthe organic layer dried over magnesium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customto give a white solid
7. temperatureAfter heating
8. temperatureat reflux for 2 hours
9. customThe layers were separated
10. extractionthe aqueous layer extracted with dichloromethane (2×50 ml)
11. dry with materialThe combined organics were dried over magnesium sulfate
12. filtrationfiltered
13. concentrationconcentrated in vacuo
14. customto give an orange solid
15. additionadded
16. temperaturesolution heated to 80° C. for 3 hours
17. temperatureAfter cooling to room temperature
18. customa solid formed that
19. filtrationwas filtered
20. washwashed with water

ORD record

ord-79b4762b816747c8909a7fa18c427ff7

Source dataset

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08541588B2