Diisopropylamine → 3-Cyclopentyl-2-(4-methoxymethylsulfanyl-phenyl)-propionic acid

Temperature

-78 °C

A solution of diisopropylamine (0.37 mL, 2.62 mmol) in tetrahydrofuran (2 mL) was cooled to −78° C. and then treated with a 2.5M solution of n-butyllithium in hexanes (1.05 mL, 2.62 mmol). This solution was stirred at −78° C. for 30 min and then treated with a solution of (4-methoxymethylsulfanyl-phenyl)-acetic acid (223 mg, 1.05 mmol) in tetrahydrofuran (1.5 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (0.5 mL). The reaction mixture was allowed to stir at −78° C. for 1 h. At this time, the reaction was treated with iodomethylcyclopentane (328 mg, 1.56 mmol). The reaction mixture was allowed to slowly warm to 25° C. where it was stirred for 18 h. At this time, the reaction mixture was quenched with a saturated aqueous sodium bicarbonate solution and then concentrated in vacuo. The residue was treated with a 1N aqueous sodium hydroxide solution and extracted with ethyl acetate. The aqueous layer was then acidified with concentrated hydrochloric acid. This solution was extracted with ethyl acetate. The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 12M, Silica, 80/20 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(4-methoxymethylsulfanyl-phenyl)-propionic acid (202 mg, 65%) as an off-white solid: mp 167-170° C.; EI-HRMS m/e calcd for C16H22O3S (M+) 294.1290, found 294.1288.

1. stirringto stir at −78° C. for 1 h
2. temperatureto slowly warm to 25° C. where it
3. stirringwas stirred for 18 h
4. customAt this time, the reaction mixture was quenched with a saturated aqueous sodium bicarbonate solution
5. concentrationconcentrated in vacuo
6. additionThe residue was treated with a 1N aqueous sodium hydroxide solution
7. extractionextracted with ethyl acetate
8. extractionThis solution was extracted with ethyl acetate
9. dry with materialThe combined organic extracts were dried over magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated in vacuo

ORD record

ord-9cc9bf49ceca49d9ad625536ee419e97

Source dataset

uspto-grants-2005_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06951945B2