Hydrochloric Acid → 4-(3,4-Dichlorophenyl)butanenitrile

Intermediate 17A (2.0 g, 9.8 mmol) was dissolved in pyridine (20 mL) and treated with methane sulfonyl chloride (0.84 mL, 10 mmol) drop wise while maintaining the temperature below 20° C. The reaction mixture was stirred at rt for 3 h and added to concentrated HCl (10 mL) in crushed ice. The layers were separated and the aqueous layer was extracted with ethyl acetate twice. The combined organic layers were washed with saturated NaHCO3 twice and brine and the organic portion dried over Na2SO4, filtered and concentrated. The resulting light yellow sulfonate ester was immediately dissolved in DMF (20 mL) and water (4 mL) and cooled to 0° C. Solid potassium cyanide (0.95 g, 15 mmol) was added to the reaction mixture and the mixture was stirred at rt for 72 h. The reaction mixture was then diluted with water and the aqueous phase extracted with ethyl acetate twice. The combined organic layers were washed with H2O twice, brine twice, dried over Na2SO4, filtered and concentrated. The residue was purified by ISCO chromatography (EtOAc/Hexanes 0-80%, column 80 g) to give Intermediate 17B (1.06 g, 24.8 mmol, 51.0%) as a white solid. HPLC/MS (Method L) RT=1.952 min, [M+1]+=214.0.

1. temperaturewhile maintaining the temperature below 20° C
2. customThe layers were separated
3. extractionthe aqueous layer was extracted with ethyl acetate twice
4. washThe combined organic layers were washed with saturated NaHCO3 twice
5. dry with materialbrine and the organic portion dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. dissolutionThe resulting light yellow sulfonate ester was immediately dissolved in DMF (20 mL)
9. temperaturewater (4 mL) and cooled to 0° C
10. stirringthe mixture was stirred at rt for 72 h
11. extractionthe aqueous phase extracted with ethyl acetate twice
12. washThe combined organic layers were washed with H2O twice
13. dry with materialbrine twice, dried over Na2SO4
14. filtrationfiltered
15. concentrationconcentrated
16. customThe residue was purified by ISCO chromatography (EtOAc/Hexanes 0-80%, column 80 g)

ORDレコード

ord-660f5b2394ee476f9eb0d7dfa6510a30

出典データセット

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08952180B2