Diiodomethane → 1-(4-Fluoro-benzoyl)-3-iodomethyl-pyrrolidine-3-carboxylic acid ethyl ester

Temperature

-78 °C

To a stirred solution of 1-(4-fluoro-benzoyl)-pyrrolidine-3-carboxylic acid ethyl ester (4.20 g, 15.8 mmol) (see Preparation 3) in tetrahydrofuran (50 mL) at −78° C. under a nitrogen atmosphere, was added lithium bis(trimethylsilyl)amide (19.0 mL of a 1.0M solution in tetrahydrofuran, 19.0 mmol). The resulting mixture was stirred at −78° C. for 30 minutes and then diiodomethane was added (1.40 mL, 17.4 mmol). The mixture was allowed to warm to room temperature and stir for a further 16 hours. The mixture was quenched with 10% aqueous citric acid (50 mL) and extracted with ethyl acetate (2×100 mL). The combined organics were washed with brine (100 mL), dried over magnesium sulphate, filtered and concentrated under reduced pressure. The crude material was purified using silica gel column chromatography, using a gradient eluent of 30% ethyl acetate in heptane to 50% ethyl acetate in heptane to afford the title compound as a colourless oil (4.2 g, 65%).

1. temperatureto warm to room temperature
2. stirringstir for a further 16 hours
3. customThe mixture was quenched with 10% aqueous citric acid (50 mL)
4. extractionextracted with ethyl acetate (2×100 mL)
5. washThe combined organics were washed with brine (100 mL)
6. dry with materialdried over magnesium sulphate
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe crude material was purified

ORD record

ord-564804a1ed04492f97ff217203e9f8e6

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08278343B2