Diisopropylamine → 2-(3,4-Dichloro-phenyl)-3-(tetrahydro-furan-2-yl)-propionic acid methyl ester

Temperature

-78 °C

A solution of diisopropylamine (0.59 mL, 4.51 mmol) in tetrahydrofuran (30 mL) was cooled to −78° C. under an argon atmosphere and then was treated with a 2.5M solution of n-butyllithium in hexanes (1.8 mL, 4.51 mmol). The reaction mixture was stirred at −78° C. for 15 min, after which time, a solution of (3,4-dichloro-phenyl)-acetic acid methyl ester (825 mg, 3.76 mmol) in tetrahydrofuran (3 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (1 mL) was slowly added via a cannula. The bright yellow solution was allowed to stir at −78° C. for 1 h, after which time, a solution of 2-iodomethyl-tetrahydro-furan (798 mg, 3.76 mmol) in 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (0.5 mL) was added via a cannula. The reaction mixture was stirred at −78° C. for 1 h and then allowed to warm to 25° C., where it was stirred for 14 h. The reaction mixture was then quenched by the addition of a saturated aqueous ammonium chloride solution (20 mL) and extracted with ethyl acetate (3×20 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 90/10 hexanes/ethyl acetate) afforded 2-(3,4-dichloro-phenyl)-3-(tetrahydro-furan-2-yl)-propionic acid methyl ester (501 mg, 44%) as a colorless oil: EI-HRMS m/e calcd for C14H16Cl2O3 (M+) 302.0477, found 302.0464.

1. stirringto stir at −78° C. for 1 h
2. stirringThe reaction mixture was stirred at −78° C. for 1 h
3. temperatureto warm to 25° C.
4. stirringwhere it was stirred for 14 h
5. customThe reaction mixture was then quenched by the addition of a saturated aqueous ammonium chloride solution (20 mL)
6. extractionextracted with ethyl acetate (3×20 mL)
7. dry with materialThe combined organic layers were dried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo

ORD record

ord-91ba3370ad9746a19a0a960294c777f9

Source dataset

uspto-grants-2006_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07105671B2