Hydrochloric Acid → 3-(4'-Fluoro-biphenyl-4-yloxymethyl)-pyrrolidine-3-carboxylic acid ethyl ester

Temperature

0 °C

6M HCl aqueous solution (65 mL) was added to racemic 1-(4-fluoro-benzoyl)-3-(4′-fluoro-biphenyl-4-yloxymethyl)-pyrrolidine-3-carboxylic acid ethyl ester (see Preparation 62) (6.3 g, 13.5 mmol) and the resulting mixture refluxed for 18 hours. The reaction mixture was evaporated to dryness. The resulting crystalline solid was dissolved in ethanol (25 mL), cooled to 0° C. and thionyl chloride added (1.46 mL, 19.81 mmol). The mixture was then heated at reflux for 16 hours. The mixture was partitioned between saturated sodium hydrogen carbonate solution (100 mL) and ethyl acetate (100 mL). The organic layer was separated, washed with water (100 mL), dried over magnesium sulphate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with 2% methanol in dichloromethane to afford the title compound as a brown oil (2.5 g, 52%).

1. temperaturethe resulting mixture refluxed for 18 hours
2. customThe reaction mixture was evaporated to dryness
3. dissolutionThe resulting crystalline solid was dissolved in ethanol (25 mL)
4. additionthionyl chloride added (1.46 mL, 19.81 mmol)
5. temperatureThe mixture was then heated
6. temperatureat reflux for 16 hours
7. customThe mixture was partitioned between saturated sodium hydrogen carbonate solution (100 mL) and ethyl acetate (100 mL)
8. customThe organic layer was separated
9. washwashed with water (100 mL)
10. dry with materialdried over magnesium sulphate
11. concentrationconcentrated under reduced pressure
12. customThe residue was purified by column chromatography on silica gel
13. washeluting with 2% methanol in dichloromethane

ORD record

ord-dea9d0a1c93149e7bd59cee174dc5d3a

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08278343B2