Dimethyl Sulfate → 4-Bromo-5,6-dimethyl-pyridine-2-carbonitrile

Temperature

70 °C

A mixture of 4-bromo-2,3-dimethyl-1-oxido-pyridin-1-ium (15.8 g, 78.2 mmol) (which may be prepared as described in Description 5) and dimethyl sulfate (8.88 mL, 93.84 mmol) in MeCN (36 mL) was stirred at block temp of 70° C. under N2 for 3.25 h. The reaction mixture was evaporated to an oil which was stirred with Et2O (2×50 ml) and the solvent was decanted from the oil. The oil was dried in vacuo and dissolved in water (105 mL) and then was added over 25 mins to a stirred solution of potassium cyanide (20.37 g, 312.79 mmol) in water (75 mL), cooled in a salt-ice Dewar bath (range during addition −5 to 0° C.). The turbid mixture was stirred in the ice/salt bath whilst it warmed slowly to ambient temperature overnight. The beige precipitate was then filtered under suction and washed with water (3×50 ml) and pressed dry. This moist solid was then dissolved in DCM (300 ml), dried (Na2SO4), filtered and evaporated to a beige solid, approximately 90% pure 4-bromo-5,6-dimethyl-pyridine-2-carbonitrile (D144) by NMR;

1. customThe reaction mixture was evaporated to an oil which
2. stirringwas stirred with Et2O (2×50 ml)
3. customthe solvent was decanted from the oil
4. customThe oil was dried in vacuo
5. dissolutiondissolved in water (105 mL)
6. temperaturewarmed slowly to ambient temperature overnight
7. filtrationThe beige precipitate was then filtered under suction
8. washwashed with water (3×50 ml)
9. custompressed dry
10. dissolutionThis moist solid was then dissolved in DCM (300 ml)
11. dry with materialdried (Na2SO4)
12. filtrationfiltered
13. customevaporated to a beige solid, approximately 90% pure 4-bromo-5,6-dimethyl-pyridine-2-carbonitrile (D144) by NMR

ORD record

ord-ca099a61d3324750948996e15444c424

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09376436B2