Acetyl chloride → 5-Chloroisatoic anhydride

Temperature

50 °C

2-Amino-6-chlorobenzoic acid (30 g) was suspended in 1,4-dioxane (225 ml) and ethyl chloroformate (75 ml) was added. The mixture was heated at reflux for 1 hour, then cooled to 50° C. and acetyl chloride (75 ml) was added. The mixture was stirred for 10 hours, after which the precipitated product was filtered off and washed with toluene. Drying in vacuum yields 5-chloroisatoic anhydride (33 g, 97% yield). 5-Chloroisatoic anhydride (30 gram) was dissolved in dimethylacetamide (300 ml), and cooled to 5° C. over a nitrogen atmosphere. Sodium hydride (5.8 g, 70%) was added portionwise, followed by addition of methyl iodide (11.5 ml). The reaction mixture was stirred at room temperature for 18 hours and the evacuated (40 mbar) for 1 hour in order to remove excess methyl iodide. Sodium hydride (5.8 g, 70%) was added followed by addition of dimethyl malonate (20 ml), and the mixture was heated to 85° C. After 3 hours at 85° C., the mixture was cooled and diluted with cold water (2.4 litre). The product was precipitated by addition of 5 M HCl (aq) until pH=1.5-2. Filtration of the precipitated product and recrystallisation from methanol gave the title compound (29 g, 70% yield).

1. temperatureThe mixture was heated
2. temperatureat reflux for 1 hour
3. filtrationafter which the precipitated product was filtered off
4. washwashed with toluene
5. customDrying in vacuum

ORD record

ord-cde5a4664a214261b4a3a3555fafc6e2

Source dataset

uspto-grants-2005_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06875869B2