Hydrochloric Acid → Diethyl 3-cyano-3-(3,4-dichlorophenyl)pentanedioate

Temperature

-10 °C

Cool a solution of sodium bis(trimethylsilyl)amide (480 lb, 1M in THF) to about -10° C. and stir. Add a solution of 3,4-dichlorophenylacetonitrile in methyl t-butyl ether (34.5% by weight, 125 lb of solution) at such a rate that the temperature of the reaction mixture does not rise above about 10° C. Combine ethyl bromoacetate (94 lb) and methyl t-butyl ether (about 125 lb) and cool to about -18° C. and then add the solution prepared above over 60-90 minutes. After the reaction is complete, as determined by chromatography, add water (18 gal). Add a 12M aqueous hydrochloric acid solution until the pH is about 4. If the pH falls below 3, use 20% aqueous sodium hydroxide solution to raise the pH to about 4. Separate the layers and extract the organic layer with brine. Evaporate in vacuo at about 40° C. to give a residue. Combine the residue and isopropanol (about 45 lb) and evaporate invacuo at about 40° C. to give a residue. Add isopropanol (190 lb), warm to about 35° C., and then cool to about -10° C. to give a solid. Collect the solid by filtration, rinse with cold isopropanol, and centrifuge to give the title compound as a wet cake containing isopropanol.

1. customdoes not rise above about 10° C
2. additionadd the solution
3. customprepared above over 60-90 minutes
4. temperatureto raise the pH to about 4
5. customSeparate the layers
6. extractionextract the organic layer with brine
7. customEvaporate in vacuo at about 40° C.
8. customto give a residue
9. customevaporate invacuo at about 40° C.
10. customto give a residue
11. customto give a solid
12. customCollect the solid
13. filtrationby filtration
14. washrinse with cold isopropanol, and centrifuge

ORD record

ord-31747a709da7439f8f46c845c69f4fc1

Source dataset

uspto-grants-1999_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05861417