Dimethylformamide → Ethyl 2-chloro-6-methylnicotinate

Temperature

5 °C

To a mixture of 20 mL of toluene, 0.5 g of potassium acetate, 0.7 ml of triethylamine, and 4.25 g (40 mmol) of ethyl cyanoacetate at 5° C. were added dropwise 7.28 g (40 mmol) of ethyl 2,2-dichlorocyanoacetate. The resulting mixture was stirred at 5° C. for 30 min., and methyl vinyl ketone (4.2 g, 60 mmol) was added via a syringe pump in 1 h. After stirring at room temperature for 6 hours, 6.2 mL (80 mmol) of DMF was added, followed by slow addition of PCl3 (11 g, 80 mmol). Anhydrous HCl gas was bubbled in for 10 min., while keeping the reaction temperature around 65° C. After being heated at 80° C. for 1 hour, the reaction mixture was cooled, quenched with aqueous ammonium hydroxide, extracted with toluene, washed with 5% NaHCO3, and dried over MgSO4. Distillation afforded 5.83 g of the title compound. (36% yield, 112°-15° C./0.2 mm Hg).

1. stirringAfter stirring at room temperature for 6 hours
2. customAnhydrous HCl gas was bubbled in for 10 min.
3. customthe reaction temperature around 65° C
4. temperatureAfter being heated at 80° C. for 1 hour
5. temperaturethe reaction mixture was cooled
6. customquenched with aqueous ammonium hydroxide
7. extractionextracted with toluene
8. washwashed with 5% NaHCO3
9. dry with materialdried over MgSO4
10. distillationDistillation

ORD record

ord-f52badfe0875446d9fac7f63d6c46dd0

Source dataset

uspto-grants-1996_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05493028