Iodoethane → 2-(4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-phenyl)-butyric acid methyl ester

温度

-78 °C

A mixture of chiral (4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-phenyl)-acetic acid methyl ester (22 mg, 0.036 mmol) was dissolved in THF (1 mL) and cooled to −78° C., then LHMDS (1 mL, 1M in THF) was added and the mixture stirred 15 min at −78° C. Ethyl iodide (0.1 mL, 0.107 mmol) was added and stirred for 1 h at −78° C., then warmed to 1 h at room temperature. The mixture was diluted with sat'd ammonium chloride solution extracted with ethyl acetate, the organic layer was separated then concentrated under reduced pressure to afford an oil that was purified by silica column chromatography (4 g Analogix column, 1-100% EtOAc/heptane) to afford 2-(4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-phenyl)-butyric acid methyl ester as a light yellow foam (12.4 mg, 53.9%). LCMS (ES+) m/z Calcd for C34H35Cl2F2N3O3+H [(M+H)+]: 641.20. found: 642.2.

1. stirringstirred for 1 h at −78° C.
2. temperaturewarmed to 1 h at room temperature
3. extractionextracted with ethyl acetate
4. customthe organic layer was separated
5. concentrationthen concentrated under reduced pressure
6. customto afford an oil that
7. customwas purified by silica column chromatography (4 g Analogix column, 1-100% EtOAc/heptane)

ORDレコード

ord-31f42802f46144e5aeb13c36213bb7bd

出典データセット

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08354444B2