Diisopropylamine → Methyl 3-cyclopentyl-2-(4-methylsulfonylphenyl)propionate

온도

-78 °C

A mechanical stirrer was used for this reaction. A solution of diisopropylamine (29.2 mL, 0.21 mol) in dry tetrahydrofuran (186 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (62 mL) was cooled to −78° C. and then treated with a 2.5 M solution of n-butyllithium in hexanes (83.4 mL, 0.21 mol). The yellow-orange reaction mixture was stirred at −78° C. for 35 min and then slowly treated with a solution of 4-(methanesulfonyl)phenyl acetic acid methyl ester (45.35 g, 0.20 mol) in dry tetrahydrofuran (186 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (62 mL). The reaction mixture turned dark in color. The reaction mixture was then stirred at −78° C. for 50 min, at which time, a solution of iodomethylcyclopentane (50.08 g, 0.24 mol) in a small amount of dry tetrahydrofuran was added slowly. The reaction mixture was then stirred at −78° C. for 50 min, and then allowed to warm to 25° C., where it was stirred for 36 h. The reaction mixture was quenched with water (100 mL), and the resulting reaction mixture was concentrated in vacuo to remove tetrahydrofuran. The remaining residue was diluted with ethyl acetate (1.5 L). The organic phase was washed with a saturated aqueous sodium chloride solution (1×500 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 70-230 mesh, 3/1 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(4-methanesulfonylphenyl)propionic acid methyl ester (41.79 g, 68%) as a yellow viscous oil: EI-HRMS m/e calcd for C16H22O4S (M+) 310.1239, found 310.1230.

1. customA mechanical stirrer was used for this reaction
2. stirringThe reaction mixture was then stirred at −78° C. for 50 min, at which time
3. stirringThe reaction mixture was then stirred at −78° C. for 50 min
4. temperatureto warm to 25° C.
5. stirringwhere it was stirred for 36 h
6. customThe reaction mixture was quenched with water (100 mL)
7. customthe resulting reaction mixture
8. concentrationwas concentrated in vacuo
9. customto remove tetrahydrofuran
10. additionThe remaining residue was diluted with ethyl acetate (1.5 L)
11. washThe organic phase was washed with a saturated aqueous sodium chloride solution (1×500 mL)
12. dry with materialdried over sodium sulfate
13. filtrationfiltered
14. concentrationconcentrated in vacuo

ORD 기록

ord-9ef1420d477a48b5bb8572d45a8217df

출처 데이터셋

uspto-grants-2001_11

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US06320050B1