Oxalyl chloride → Methyl 3-hydroxy-2-nitrobenzoate

Temperature

40 °C

3-Hydroxy-2-nitro-benzoic acid (commercially available) (31.5 g) was suspended in acetonitrile (100 ml). Oxalyl chloride (22 ml) in acetonitrile (20 ml) was added dropwise upon which a vigorous gas stream evolved. After 15 minutes the reaction slowed down and therefore, the reaction mixture was heated with a warm water bath (40° C.) for 40 minutes. The mixture was concentrated and the residue was re-dissolved in dichloromethane (100 ml). A mixture of methanol (50 ml) and triethylamine (20 ml) in dichloromethane (30 ml) was added dropwise while cooling the mixture with an ice bath. The reaction mixture was stirred at ambient temperature for 16 hours. The mixture was concentrated and the residue was purified by column chromatography on silica gel (eluent: 10-55% v/v ethyl acetate in heptane) to give 3-hydroxy-2-nitro-benzoic acid methyl ester (15.9 g). 1H-NMR (400 MHz, CDCl3): 10.15 (bs, 1H), 7.60 (t, 1H), 7.27 (d, 1H), 7.08 (d, 1H), 3.93 (s, 3H) ppm.

1. concentrationThe mixture was concentrated
2. dissolutionthe residue was re-dissolved in dichloromethane (100 ml)
3. additionA mixture of methanol (50 ml) and triethylamine (20 ml) in dichloromethane (30 ml)
4. additionwas added dropwise
5. temperaturewhile cooling the mixture with an ice bath
6. concentrationThe mixture was concentrated
7. customthe residue was purified by column chromatography on silica gel (eluent: 10-55% v/v ethyl acetate in heptane)

ORD record

ord-a071d0eadcdf412ea7ee1a7678b8321d

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08859592B2