Sulfuric Acid → HCID 59540946, compound

Temperature

0 °C

To a tan solution of 5-chloro-2-methylsulfanyl-phenylamine (5.4 g, 31 mmol.) in THF (35 mL) and MeOH (35 mL) was added dropwise a solution of 2,5-dimethoxy-tetrahydro-furan (5.3 mL, 40 mmol) and 2.5 M H2SO4 (31 mL, 78 mmol) in THF (45 mL) via addition funnel over 1 h. The reaction was cooled to 0° C. and NaBH4 (4.7 g, 124 mmol) was added portionwise over 1 h with vigorous stirring. The reaction mixture was allowed to slowly warm to room temperature, stirred at room temperature overnight, diluted with water (60 mL), stirred at room temperature overnight, slowly basified with NaOH (˜7 g) until pH˜10 while cooling with an ice bath, and extracted with Et2O. The combined organic extracts were extracted with 6 N HCl (100 mL). The aqueous phase was basified with NaOH (˜30 g, 0.75 mmol) until pH˜10, and extracted with Et2O. The organic extract was dried with Na2SO4 and concentrated to give 2 g of the crude product. The crude product was purified by flash chromatography using 40 g of silica gel and 5-50% EtOAc in hexanes as eluant to afford 0.55 g of 1-(5-chloro-2-methylsulfanyl-phenyl)-pyrrolidine. M+H 228.

1. additionvia addition funnel over 1 h
2. temperatureto slowly warm to room temperature
3. stirringstirred at room temperature overnight
4. temperaturewhile cooling with an ice bath
5. extractionextracted with Et2O
6. extractionThe combined organic extracts were extracted with 6 N HCl (100 mL)
7. extractionextracted with Et2O
8. extractionThe organic extract
9. dry with materialwas dried with Na2SO4
10. concentrationconcentrated
11. customto give 2 g of the crude product
12. customThe crude product was purified by flash chromatography

ORD record

ord-9ddefe4e1fe648acbedd92045c844dfc

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08008298B2