Triethylamine → (+/-)-rel-1-(3-fluoro-4-methylbenzyl)-3-((3S,4S)-3-hydroxy-4-(4-methoxyphenyl)piperidin-1-yl)pyrrolidin-2-one

温度

100 °C

To a solution of 3-bromo-1-(3-fluoro-4-methylbenzyl)pyrrolidin-2-one (Intermediate 6, 200 mg, 0.7 mmol) and (±)-rel-(3S,4S)-4-(4-methoxyphenyl)piperidin-3-ol (145 mg, 0.7 mmol, from Example 46, step B) in acetonitrile (15 mL) was added triethylamine (0.1 mL, 0.7 mmol) and the resulting mixture was heated in the microwave at 100° C. for 1 h. The cooled reaction mixture was diluted with a saturated ammonium chloride solution and extracted with ethyl acetate (100 mL). The organic layer was separated, dried over Na2SO4, filtered, and evaporated under reduced pressure to give (±)-rel-1-(3-fluoro-4-methylbenzyl)-3-((3S,4S)-3-hydroxy-4-(4-methoxyphenyl)piperidin-1-yl)pyrrolidin-2-one (280 mg, 0.51 mmol, 73% yield, mixture of 4 diaseteroisomers), which was used directly in the next step. LCMS (Method F) RT 1.99 min m/z 413.2 (M+H+).

1. customThe cooled reaction mixture
2. extractionextracted with ethyl acetate (100 mL)
3. customThe organic layer was separated
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. customevaporated under reduced pressure

ORDレコード

ord-c92b7ea9cf284e9ab803350a4e40dd0a

出典データセット

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09221796B2