Producing Isoxazoline-3-yl-acyl Benzene

Patent Method for Producing Isoxazoline-3-yl-acyl Benzene 

Rheinheimer etal, US Patent 6,525,204 (February 25, 2003) Assignee BASF Aktiengesellschaft Utility Herbicide 

A solution of n-butyl nitrite (2.6 mol) and 3-nitro-o-xylene (2.0 mol) dissolved in 750 ml of dimethylformamide were cooled to -60°C and potassium t-butoxide (4.56 mol) dissolved in 750 ml of dimethylform-amide added over 3 hours. Thereafter, 300 ml water were added followed by 300 ml HOAc until a pH 5-6 reached. The mixture was then poured into 6 kg of ice water, the residue filtered, washed with water, and dried. The precipitate was placed in a suspension of about 3L of toluene at 80-90 °C 2 hours, the mixture filtered, dried, and the product isolated in 77% yield, 98% purity, mp = 190-192°C. 

At 60 °C, N-chlorosuccinimide (28 mmol) dissolved in 30 ml acetonitrile was added to the product from Step 1 (28 mmol) dissolved in 50 ml acetonitrile and the mixture stirred 20 minutes, cooled, and concentrated. The residue was suspended in 50 ml of toluene for about 90 minutes, filtered, filled into a mini autoclave, and an ethylene pressure of 30 bar applied. Over a period of 5 hours, a solution of NaHCOj (4.7 g) dissolved in 50 ml water was metered in and the mixture stirred at 30 bar ethylene pressure 5 hours. Thereafter, the phases were separated, the toluene phase washed twice with NaHCOj, once with water, dried, concentrated, and the product isolated in 86% yield, mp = 100-105 °C. H-NMR data supplied. 

A mixture consisting of the product from Step 3 (0.57 mol) was dissolved in 1.2 L EtOAc, 5% platinum on carbon (11.7 g) added, and the mixture hydrogenated at 25-30°C 48 hours at 20 bar hydrogen. Thereafter the mixture was filtered through silica gel and the solvent removed. The residue was dissolved in methyl t-butyl ether and water and extracted with IM HCl. The aqueous phase pH was adjusted to 10-11, then extracted with CH2CI2, dried, concentrated and the product isolated in 87% yield, 97% purity, mp = 86-88 °C. 

---