Reaktion #75375
ord-2783042554b5494f958a148cd2eee52e
Reaktionsgleichung
Edukte
Reagenzien
Reaktionsbedingungen
Aufarbeitung
- 1Temperaturthe resulting slurry is cooled to +3° C.
- 2workup.WAITAfter a further 15 minutes
- 3Filtrationflocks are filtered off
- 4Temperaturthe filtrate is cooled to +5° C., whereupon a dark resin
- 5Sonstigethe supernatant solution is decanted off from the resin and latter
- 6Extraktionis extracted with sodium bicarbonate solution
- 7Sonstigethe acid is precipitated
- 8Extraktionextract
- 9SonstigeFor further purification
- 10Filtrationthe dried ethyl acetate solution is filtered through a column
- 11workup.ADDITIONcontaining 35 g of silica gel
- 12Sonstigethe filtrate is evaporated in vacuo
- 13workup.ADDITIONthe temperature slowly rising during the addition
- 14workup.WAITAfter 20 minutes
- 15Temperaturthe temperature is raised to 90°-100° for 45 minutes
- 16Filtrationthe resulting suspension is then filtered
- 17Waschenthe precipitate is washed with glacial acetic acid
- 18Sonstigethe filtrate is evaporated in vacuo
- 19Extraktionextracted with ethyl acetate
- 20Einengenthe resulting solution is concentrated to a smaller volume
- 21Sonstigecrystallised
- 22workup.ADDITIONThis compound (72 g=0.25 mol) is added, under nitrogen blanketing gas, to a thiophenolate solution
- 23workup.DISSOLUTIONthe resulting suspension is dissolved
- 24Sonstigespontaneously rising to above 100°
- 25Sonstigeis kept at 110°
- 26Temperatur(reflux) for a further 5 hours
- 27Extraktionextracted three times with ethyl acetate
- 28Sonstigethe ethyl acetate layer is separated off
- 29Waschenwashed twice with sodium chloride solution
- 30Extraktionis twice extracted
- 31workup.STIRRINGby shaking with saturated sodium bicarbonate solution
- 32Extraktiontwice extracted
- 33workup.STIRRINGby shaking with water (excess thiophenol
- 34Sonstigethe precipitate which has separated out
- 35Waschenthe ethyl acetate layer is washed with water
- 36Sonstigedried
- 37Filtrationfiltered
- 38Sonstigethe filtrate is evaporated
- 39SonstigeOn grinding with a little ethyl acetate, 3-sulphamoyl-4-phenylthio-5-[β-cyanoethyl]-benzoic acid
- 40Sonstigecrystallises
Vorschrift
The starting material is accessible by the following route: 4.8 ml of concentrated hydrochloric acid and 20 ml of water are added to 3-sulphamoyl-4-chloro-5-aminobenzoic acid (P. W. Feit, H. Bruun and C. Kaergaard-Nielsen, J. Med. Chem. 13, 1,071 (1970); 5.01 g=20 mmols) and the resulting slurry is cooled to +3° C. and diazotised with 20 ml of 1 N sodium nitrite solution at 0°-5°, after which, after a total of 30 minutes, a solution of acrylonitrile (1.4 g=1.74 ml=26 mmols) in acetone (25 ml) is added to the suspension, which has become mobile, and solid CuCl2.2H2O (1 g) is added to the resulting yellow solution, carefully at first and then all at once, and the mixture is heated slowly to 35° C., with vigorous stirring, whereupon a vigorous evolution of nitrogen starts fairly suddenly; this has ended after about 15 minutes. After a further 15 minutes, flocks are filtered off and the filtrate is cooled to +5° C., whereupon a dark resin settles on the base of the flask, the supernatant solution is decanted off from the resin and latter is ground with 30 ml of water. After it has been taken up in 200 ml of ethyl acetate the acid is extracted with sodium bicarbonate solution and the acid is precipitated by acidifying the extract and is taken up in ethyl acetate again. For further purification, the dried ethyl acetate solution is filtered through a column containing 35 g of silica gel, the filtrate is evaporated in vacuo and the residue is further processed. The above crude product comprising 3-sulphamoyl-4-chloro-5-(β-chloro-β-cyanoethyl)-benzoic acid (2.7 g=8.35 mmols) is dissolved in glacial acetic acid and a total of 1.5 g of zinc dust is added in portions at room temperature, with stirring, the temperature slowly rising during the addition. After 20 minutes, the temperature is raised to 90°-100° for 45 minutes, the resulting suspension is then filtered and the precipitate is washed with glacial acetic acid and the filtrate is evaporated in vacuo. The residue is acidified with hydrochloric acid and extracted with ethyl acetate and the resulting solution is concentrated to a smaller volume and crystallised. The resulting 3-sulphamoyl-4-chloro-5-(β-cyanoethyl)-benzoic acid melts at 224°-228° C. This compound (72 g=0.25 mol) is added, under nitrogen blanketing gas, to a thiophenolate solution prepared from solid sodium hydroxide (25 g=0.625 mol), water (30 ml) and thiophenol (68.8 g=63.7 ml=0.625 mol) and the resulting suspension is dissolved by adding 150 ml of hexamethylphosphoric acid triamide, the temperature spontaneously rising to above 100°. The mixture is kept at 110° (reflux) for a further 5 hours and is then poured into 300 ml of water, rendered strongly acid (Congo red) with 6 N hydrochloric acid and extracted three times with ethyl acetate, the ethyl acetate layer is separated off and washed twice with sodium chloride solution and is twice extracted by shaking with saturated sodium bicarbonate solution and twice extracted by shaking with water (excess thiophenol remains in the ethyl acetate phase), the combined bicarbonate and water phases are acidified, the precipitate which has separated out is again taken up in ethyl acetate, the ethyl acetate layer is washed with water, dried and filtered and the filtrate is evaporated. On grinding with a little ethyl acetate, 3-sulphamoyl-4-phenylthio-5-[β-cyanoethyl]-benzoic acid crystallises; pale yellow crystals from ethyl acetate/ether, melting point 179°-181° C.