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

Temperature

15 °C

5-hydroxy-4-methoxy-2-nitrobenzoic acid (31.9 g, 0.15 mol, 1.0 eq) and 2-methyltetrahydrofuran (200 mL) are charged into a glass reactor under nitrogen. The solution is stirred and jacket temp is set to 20° C. Oxalyl chloride (24 g, 0.19 mol, 1.25 eq) is added at a rate that the internal temperature is below 25° C. The reaction mixture is stirred for 1-2 hour at 20° C., and cooled to 15° C. Then, anhydrous MeOH (60 ml, 1.5 mol, 10 eq) is added over 15 min, and the reaction temperature is maintained below 25° C. during addition. The reaction mixture is stirred for 2-4 hour at 20° C. until HPLC sample shows complete conversion. Na2CO3 aqueous solution (1 M, 100 ml) is added to the reaction mixture. Layers are separated. The upper organic layer is distilled under vacuum to minimum volume. The dark brown residue is stirred in 100 mL mixed solvent of toluene/hexane (v/v, 2:1) to give a suspension. The slurry is filtered. The solid is dried under vacuum to provide the desired product, methyl 5-hydroxy-4-methoxy-2-nitrobenzoate (31.3 g, 92% yield).

1. customis set to 20° C
2. customis below 25° C
3. stirringThe reaction mixture is stirred for 1-2 hour at 20° C.
4. temperaturethe reaction temperature is maintained below 25° C. during addition
5. stirringThe reaction mixture is stirred for 2-4 hour at 20° C. until HPLC sample
6. customLayers are separated
7. distillationThe upper organic layer is distilled under vacuum to minimum volume
8. stirringThe dark brown residue is stirred in 100 mL
9. additionmixed solvent of toluene/hexane (v/v, 2:1)
10. customto give a suspension
11. filtrationThe slurry is filtered
12. customThe solid is dried under vacuum

ORD record

ord-2ae8ca4564b240ceaec8a18181a29edf

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08519176B1