Acetyl chloride → (6R)-7-amino-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Temperature

-15 °C

To a slurry of 3.40 gm (10 mmol) of 7-phenoxyacetamido-3-methyl-3-cephem-4-carboxylic acid, 0.158 ml (1.34 mmol) of quinoline, and 2.38 ml (15 mmol) of N,N-diethylaniline in 30 ml. of methylene chloride at room temperature was added 2.46 ml (34.5 mmol) of acetyl chloride. The reaction mixture was allowed to stir for about 6 hours at a temperature of 18° to 22° C. The reaction mixture was then cooled to -15° C. Then 0.6 ml (3.75 mmol) of N,N-diethylaniline and a solution of the triphenyl phosphitechlorine reagent derived from 3.68 ml of triphenyl phosphite and chlorine in 15 ml of methylene chloride, were added. The reaction mixture was then removed from the cooling bath and allowed to warm to near room temperature over the next seven minutes. The reaction mixture was then cooled to -20° C. Then 10.7 ml (116 mmol) of isobutanol added. Again the reaction mixture was removed from the cooling bath. About 45 minutes after the addition of the alcohol, a copious amount of solid precipitate was observed. After an additional 1/2 hour at room temperature the reaction mixture was cooled to 0° C. and filtered to provide 1.95 gm (73%) of 7-ADCA. Some impurities were visible in an nmr spectrum of the product.

1. additionwere added
2. customThe reaction mixture was then removed from the cooling bath
3. temperatureto warm
4. customto near room temperature over the next seven minutes
5. temperatureThe reaction mixture was then cooled to -20° C
6. customAgain the reaction mixture was removed from the cooling bath
7. additionAbout 45 minutes after the addition of the alcohol
8. temperatureAfter an additional 1/2 hour at room temperature the reaction mixture was cooled to 0° C.
9. filtrationfiltered

ORD record

ord-9591e1bd219c4f1880a5cde6b3fa4d78

Source dataset

uspto-grants-1980_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04211702