Acetyl chloride → Acetic-formic anhydride

To a stirred suspension of 130 g anhydrous sodium formate (1.91 M) in 60 ml ethyl acetate at 20° C. was added 99 g acetyl chloride (1.26 M) and the white suspension stirred for 6 h. The mixture was filtered and the solids washed twice with 25 ml ethyl acetate. The combined filtrate and rinse were analyzed by 300 MHz proton NMR. Integration of peaks at 2.25, 8.75, and 9.1 gave the following composition in mol %: 3% acetic-anhydride, 3.5% formic anhydride, 30% formic-acetic anhydride. To 193 g of the above solution at −5° C. were added 22 g of 2,4,6-trihydroxyphenyl-4′-hydroxybenzyl ketone (84.5 mM) followed by a drop by drop addition of 118 g di-isopropylethylamine (1.01 M) over 60 min and the reaction stirred at −5° C. for 18 h. To the yellowish solution was added 100 ml hydrochloric acid (37%) and the mixture heated to 90° C. under 150 mbar vacuum to remove approximately 115 g of distillate. To the residue was added 225 ml water causing crystallization. The slurry was cooled, held at 0° C. for 30 min followed by filtration. The solids were rinsed twice with 100 ml water and dried at 25 mbar for 6 h at 60° C. to obtain a white powder (19.6 g). Quantitative HPLC analysis with external standards showed this to contain 97.3 wt. % genistein and 2.5 wt. % 2-methylgenistein. The yield of genistein is therefore 79% based on the ketone.

1. filtrationThe mixture was filtered
2. washthe solids washed twice with 25 ml ethyl acetate
3. washThe combined filtrate and rinse

ORD record

ord-25623e7cb3a747d9bd01110086a240d3

Source dataset

uspto-grants-2006_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07109358B2