Sodium saccharine (commercial grade),
Methyl chloroacetate (Alfa Aesar),
Anhydrous DMF (sigma aldrich)

Anhydrous DMF (15 mL) was added to sodium saccharine (20.0g, 98 mmoles) in a round bottom flask, under a balloon of nitrogen, and stirred at 120⁰C for 15 minutes to give a white suspension. Methyl chloroacetate (98 mmoles) was then added dropwise and the resulting clear solution stirred for a further 45 minutes. The reaction mixture was cooled to room temperature and then poured over crushed ice. The resulting white precipitate was filtered under suction, washed with excess cold water and dried to yield the product as a white solid. Yield: 23.2g, 94%

The product formed is a starting material for the anti-inflammatory drugs Piroxicam, Isoxicam and Sudoxicam. The anhydrous conditions are extremely important to get best yields. We carried out the reaction successfully on different scales eg 50-100g. In general, these reaction conditions are applicable for the N-alkylation of amines, but in those cases, any mild base like Sodium carbonate or Potassium carbonate must be used in order to neutralize the acid formed as byproduct.

M.Pt : 116 ⁰C, IR (KBr): 1755, 1344, 1189 cm^-1, MS m/z: 255 (M+), ¹HNMR (CDCl₃: 3.80(s, 3H), 4.45(s, 2H), 7.79(dd, J = 5.6, 3.2 HZ, 2H), 7.82(dd, J=5.5, 3.2HZ, 2H)

N.Manjarrez, H.I.Perez, A.Solis, Hector Luna, Synthetic Communications 1996,26, 585-591

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