Methanol → Methyl 4-fluoro-5-hydroxy-2-nitrobenzoate

Temperature

12.5 °C

Starting material 4-fluoro-5-hydroxy-2-nitrobenzoic acid, 68 g, 0.34 mol, 1.0 eq) and methanol (140 mL) were charging into a reactor under nitrogen. The solution was cooled to 10-15° C. Sulfuric acid (120 g, 1.2 mol, 3.5 eq) was added at a rate that the internal temperature was below 30° C. The reaction mixture was'refluxed at 65-75° C. for 12-15 hour until HPLC sample showed the conversion was higher than 96%. The mixture was concentrated to minimum volume and the residue was charged into cold water (400 mL) slowly so that the batch was kept below 25° C. The resulting suspension was stirred at 10-15° C. for about 2 hours. The slurry was filtered. The desired product, methyl 4-fluoro-5-hydroxy-2-nitrobenzoate, was obtained as a light brown solid after drying under vacuum (62 g, 85% yield). 1H NMR (CDCl3, 400 MHz) δ 7.84 (d, J=9.7 Hz, 1H), 7.25 (d, J=8.4 Hz, 1H), 6.66 (s, 1H), 3.93 (s, 3H). 13C NMR (DMSO-4, 100 MHz) δ 165.3, 157.6, 151.9, 151.0, 150.8, 149.4, 138.0, 137.9, 125.9, 117.4, 114.1, 113.8, 53.3.

1. customwere charging into a reactor under nitrogen
2. customwas below 30° C
3. concentrationThe mixture was concentrated to minimum volume
4. additionthe residue was charged into cold water (400 mL) slowly so that the batch
5. customwas kept below 25° C
6. filtrationThe slurry was filtered

ORD record

ord-337afcfdfe4b457eb5fb231b2cb635ca

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08519176B1