4-(Acetylamino)phenyl chloroacetate synthesis

Yield:17321-63-0 72%

Reaction Conditions:

with pyridine in acetone at 0 - 20;Inert atmosphere;

Steps:

30

Paracetamol [1] (15.117 g, 50 mmol) and pyridine (7.910 g, 50 mmol) were suspended in anhydrous acetone (200 ml) and chilled to 0 °C under an atmosphere of dry nitrogen. Chloroacetylchloride (11.29 g, 50 mmol) was added dropwise (violent reaction) and the resulting solution was stirred for additional 2 hours at room temperature. Water (300 ml) was added and the mixture was heated until a clear solution was obtained. The product [2] precipitated upon cooling and was collected via filtration, washed with water and dried under reduced pressure (0.01 mbar, 50 °C) to yield [2] as colourless needles in 72% yield. The product was pure according to ¹H NMR and directly subjected to the next step without further purification.¹H-NMR (300 MHz, d₆-DMSO) δ(ppm) = 10.05 (s, IH), 7.62 (d, J = 9.01 Hz, 2H), 7.10 (d, J = 9.01 Hz, 2H), 4.67 (s, 2H), 3.38 (s, 3H), 2.05 (s, 3H). ¹³C-NMR (75 MHz, d₆-DMSO) δ(ppm) = 168.7, 166.9, 145.6, 137.2, 122.0, 120.3, 41.6, 24.3. mp 186 ⁰C

References:

WO2010/78300,2010,A1 Location in patent:Page/Page column 106; 107