2,4-dioxo-4-pyridin-4-yl-butyric acid ethyl ester synthesis

Yield:60943-41-1 98%

Reaction Conditions:

Stage #1: methyl (4-pyridyl) ketonewith lithium hexamethyldisilazane in diethyl ether at -78; for 0.75 h;
Stage #2: oxalic acid diethyl ester in diethyl ether at -78 - 27; for 16.5 h;

Steps:

[0202] Preparation of ethyl 2,4-dioxo-4-(pyridin-4-yl)butanoate (B-2)

[0202] Preparation of ethyl 2,4-dioxo-4-(pyridin-4-yl)butanoate (B-2): A solution of 4- acteyl pyridine (10.0 g, 82.55 mmol) in diethyl ether (160 mL) was cooled to -78°C followed by addition of LiHMDS (15.16 g, 90.80 mmol). The resulting reaction mixture was stirred at -78°C for 45 min followed by drop wise addition of diethyl oxalate in about 30min. The reaction mixture was then left to stir at room temperature for 16 h. After completion of the reaction (TLC and MS monitoring), the solution was then cooled 0°C and the resulting precipitate was filtered to get the desired product as an off-white solid (18.0 g, 98%), which was carried forward to the next step without purification. [0203] 1H-NMR (400 MHz, DMSO-d₆): δ 8.66 (d, J= 4.80 Hz, 2H), 7.70 (d, J= 5.20 Hz, 2H), 6.43 (s, 1H), 4.15 (q, J= 7.20 Hz, 2H) and 1.25 (t, J= 7.20 Hz, 3H).

References:

WO2015/103060,2015,A1 Location in patent:Paragraph 0202-0203