Diisopropylamine → 2-(4-Methanesulfonyl-phenyl)-3-[2-(tetrahydropyran-2-yloxy)-cyclopentyl]-propionic acid methyl ester

온도

-78 °C

A solution of diisopropylamine (846 μL, 6.04 mmol) in dry tetrahydrofuran (4.4 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (1.4 mL) was cooled to −78° C. and then treated with a 2.5M solution of n-butyllithium in hexanes (2.4 mL, 6.04 mmol). The reaction mixture was stirred at −78° C. for 30 min and then was treated with a solution of (4-methanesulfonyl-phenyl)-acetic acid methyl ester (prepared as in Example 8, 1.06 g, 4.64 mmol) in dry tetrahydrofuran (4.4 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (1.4 mL). The resulting reaction mixture was allowed to stir at −78° C. for 45 min and then the reaction mixture was treated with a solution of 2-(2-iodomethyl-cyclopentyloxy)-tetrahydropyran (prepared as in Example 24, 1.87 g, 6.04 mmol) in a small amount of dry tetrahydrofuran. The reaction mixture was stirred at −78° C. and then allowed to warm to 25° C., where it was stirred for 68 h. The reaction mixture was quenched with water (100 mL) and then concentrated in vacuo to remove tetrahydrofuran. The aqueous residue was extracted with ethyl acetate (2×100 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 70–230 mesh, 7/3 hexanes/ethyl acetate) afforded the 2-(4-methanesulfonyl-phenyl)-3-[2-(tetrahydropyran-2-yloxy)-cyclopentyl]-propionic acid methyl ester (859.2 mg, 45%) as a light yellow oil: FAB-HRMS m/e calcd for C21H30O6S (M+H)+ 411.1841, found 411.1831.

1. customThe resulting reaction mixture
2. stirringto stir at −78° C. for 45 min
3. stirringThe reaction mixture was stirred at −78° C.
4. temperatureto warm to 25° C.
5. stirringwhere it was stirred for 68 h
6. customThe reaction mixture was quenched with water (100 mL)
7. concentrationconcentrated in vacuo
8. customto remove tetrahydrofuran
9. extractionThe aqueous residue was extracted with ethyl acetate (2×100 mL)
10. dry with materialThe combined organic extracts were dried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated in vacuo

ORD 기록

ord-bfec7163ceaf405cbd4edabcad82506b

출처 데이터셋

uspto-grants-2006_09

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07105671B2