General procedure for the synthesis of methyl 2-chloro-3-nitrobenzoate from methanol and 2-chloro-3-nitrobenzoic acid:
1. to a solution of 2-chloro-3-nitrobenzoic acid (10.0 g, 49.6 mmol) in methanol (80 mL) was added concentrated sulfuric acid (2.0 mL).
2. The reaction mixture was stirred overnight under reflux conditions.
3. Upon completion of the reaction, the methanol was removed by vacuum concentration.
4. Water was added to the residue and extracted with ethyl acetate.
5. The organic phase was washed sequentially with water, saturated sodium bicarbonate solution and saturated brine. 6.
6. The organic phase was dried with magnesium sulfate.
7. The target compound, methyl 2-chloro-3-nitrobenzoate (10.6 g, 99% yield), was obtained as a white solid by vacuum concentration.
8. The product was characterized by 1H NMR (CDCl3) and HPLC: 1H NMR (CDCl3) δ (ppm): 7.95 (dd, 1H), 7.84 (dd, 1H), 7.48 (t, 1H), 3.98 (s, 3H). HPLC Rt = 11.88 min. 150 × 6.0 mm); mobile phase: 0-20 min, acetonitrile/water = 10/90 to 100/0 (gradient), 20-30 min, acetonitrile/water = 100/0 (isocratic); flow rate: 1 mL/min.
