Diisopropylamine → HCID 67482158, compound

Temperature

-78 °C

A solution of diisopropylamine (1.21 mL, 8.62 mmol) in dry tetrahydrofuran (30 mL) was cooled to −78° C. under argon and was then treated with a 2.5M solution of n-butyllithium in hexanes (3.3 mL, 8.25 mmol). The reaction mixture was stirred at −78° C. for 30 min and then treated dropwise with a solution of (4-methylsulfanyl-phenyl)-acetic acid methyl ester (1.47 g, 7.5 mmol) in dry tetrahydrofuran (10 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (3.34 mL). The reaction mixture turned gold in color and was allowed to stir at −78° C. for 1 h. The reaction mixture was then treated with a solution of trifluoromethanesulfonic acid (R)-tetrahydro-furan-2-yl methyl ester (2.30 g, 9.8 mmol) in dry tetrahydrofuran (10 mL). The reaction mixture was allowed to warm to 25° C., where it was stirred for 16 h. The reaction mixture was quenched with a saturated aqueous ammonium chloride solution (30 mL) and then concentrated in vacuo to remove tetrahydrofuran. The aqueous residue was extracted with ethyl acetate (3×75 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 9/1 hexanes/ethyl acetate) afforded 2-(4-methylsulfanyl-phenyl)-3-(tetrahydro-furan-2(R)-yl)-propionic acid methyl ester (0.810 g, 39%) as a pale yellow oil: [α]23589=−10.87° (c=0.46, chloroform); EI-HRMS m/e calcd for C15H20O3S (M+) 280.1133, found 280.1130.

1. stirringto stir at −78° C. for 1 h
2. temperatureto warm to 25° C.
3. stirringwhere it was stirred for 16 h
4. customThe reaction mixture was quenched with a saturated aqueous ammonium chloride solution (30 mL)
5. concentrationconcentrated in vacuo
6. customto remove tetrahydrofuran
7. extractionThe aqueous residue was extracted with ethyl acetate (3×75 mL)
8. dry with materialThe combined organic extracts were dried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo

ORD record

ord-8fb06432d2f948f6a67f1415b9c52e2e

Source dataset

uspto-grants-2006_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07105671B2