Diisopropylamine → 3-Cyclopentyl-2-(3-trifluoromethylsulfanyl-phenyl)-propionic acid methyl ester

온도

-78 °C

A solution of diisopropylamine (1.5 mL, 10.5 mmol) in dry tetrahydrofuran (27 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (8 mL) was cooled to −78° C. under nitrogen and then treated with a 2.5M solution of n-butyllithium in hexanes (4.2 mL, 10.5 mmol). The resulting reaction mixture was stirred at −78° C. for 30 min and then treated dropwise with a solution of (3-trifluoromethylsulfanyl-phenyl)-acetic acid methyl ester (2.50 g, 10.0 mmol) in a small amount of tetrahydrofuran. The reaction mixture was allowed to stir at −78° C. for 1 h, at which time, a solution of iodomethylcyclopentane (2.10 g, 10.0 mmol) in a small amount of dry tetrahydrofuran was added dropwise. The reaction mixture was allowed to warm to 25° C. where it was stirred for 15 h. The reaction mixture was quenched with water (50 mL) and then partitioned between water (75 mL) and ethyl acetate (75 mL). The layers were shaken and separated. The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 8/1 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(3-trifluoromethylsulfanyl-phenyl)-propionic acid methyl ester (2.95 g, 89%) as a colorless oil: EI-HRMS m/e calcd for C16H19F3O2S (M+) 332.1058, found 332.1047.

1. customThe resulting reaction mixture
2. stirringto stir at −78° C. for 1 h, at which time
3. temperatureto warm to 25° C. where it
4. stirringwas stirred for 15 h
5. customThe reaction mixture was quenched with water (50 mL)
6. custompartitioned between water (75 mL) and ethyl acetate (75 mL)
7. stirringThe layers were shaken
8. customseparated
9. dry with materialThe organic layer was dried over magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated in vacuo

ORD 기록

ord-222609b018c348ea80441e9ae2a8ac3f

출처 데이터셋

uspto-grants-2007_05

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07223868B2