Iodoethane → Methyl (3S*,4R*)-4-(2,4-difluorophenyl)-1-ethylpyrrolidine-3-carboxylate

To a stirred solution of methyl (3S,4R)-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylate, from preparation 19 (10.5 g, 43 mmol) in tetrahydrofuran (215 mL) at room temperature under dry nitrogen was added iodoethane (3.8 mL, 48 mmol) and N,N-diisopropylethylamine (8.3 mL, 48 mmol) in single portions. The resulting mixture was stirred at room temperature under dry nitrogen for 72 hours, then quenched by the addition of water (200 mL) and extracted with ethyl acetate (2×250 mL). The combined organic layers were dried (magnesium sulfate), filtered, and concentrated in vacuo. The residue was purified by flash column chromatography eluting with a 2:1 pentane:ethyl acetate mixture increasing polarity to 1:1. This afforded the title compound as a clear oil (7.9 g, 68%).

1. customquenched by the addition of water (200 mL)
2. extractionextracted with ethyl acetate (2×250 mL)
3. dry with materialThe combined organic layers were dried (magnesium sulfate)
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe residue was purified by flash column chromatography
7. washeluting with a 2:1 pentane
8. temperatureethyl acetate mixture increasing polarity to 1:1

ORD record

ord-8d8b71b26c6645308e3ac21c51cd9f83

Source dataset

uspto-grants-2010_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07649002B2