Diethyl 2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]malonate synthesis

Yield:172527-71-8 89%

Reaction Conditions:

with sodium hydroxide in N,N-dimethyl acetamide at 20 - 70; for 3 h;Product distribution / selectivity;

Steps:

4.2

Example 2; A two-necked round bottom flask equipped with a magnetic bar, a thermometer and an addition funnel was charged with 2,3-dichloro 5-trifluoromethyl pyridine (5.4 g, 25 mmol), DMAC (20 ml) and NaOH (2.4 g, 40 mmol). Diethyl malonate (4.8 g, 30 mmol) was slowly added at 20° C. The temperature was raised to 70° C. and the reaction mixture was agitated for 3 hours at 70° C. Then the reaction mixture was cooled to room temperature and mixed with 200 ml of water. This mixture was extracted with CH₂Cl₂ and the organic phase washed with water. The organic phase was dried over MgSO₄ and concentrated under vacuum. 9.66 g of an orange oil were obtained. Purity (GC): 78.7% (16.3% DMAC), giving an isolated yield of about 89%. Mass spectrum: [M+1]=340 (³⁵Cl) Boiling point=87-90° C./0.06-0.07 mbar. Melting point: 45.5-47° C. (cyclohexane). NMR¹H(CDCl₃, 400 MHz): 1.30 (t, 6H, 2CH₃); 4.31 (m, 4H, 2CH₂); 5.25 (s, 1H, CH); 7.96 (d, 1H, Haro); 8.76 (d, 1H, Haro).

References:

US2008/86008,2008,A1 Location in patent:Page/Page column 12