Diisopropylamine → HCID 67482102, compound

Temperature

-78 °C

A solution of diisopropylamine (1.86 mL, 13.29 mmol) in dry tetrahydrofuran (45 mL) cooled to −78° C. under argon was treated with a 2.5M solution of n-butyllithium in hexanes (5.10 mL, 12.75 mmol). The reaction mixture was stirred at −78° C. for 30 min and then was treated dropwise with a solution of (4-fluoro-3-trifluoromethyl-phenyl)-acetic acid methyl ester (2.51 g, 10.63 mmol) in dry tetrahydrofuran (15 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (6.5 mL). The reaction mixture turned gold in color and was allowed to stir at −78° C. for 1 h. At this time, the reaction was treated with a solution of trifluoromethanesulfonic acid (R)-tetrahydro-furan-2-yl methyl ester (prepared as in Example 3, 3.23 g, 13.81 mmol) in dry tetrahydrofuran (15 mL). The reaction mixture was allowed to warm to 25° C., where it was stirred for 16 h. The reaction mixture was then quenched with a saturated aqueous ammonium chloride solution (30 mL) and was then concentrated in vacuo to remove tetrahydrofuran. The aqueous residue was extracted with ethyl acetate (3×150 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 85/15 hexanes/ethyl acetate) afforded 2-(4-fluoro-3-trifluoromethyl-phenyl)-3-(tetrahydro-furan-2(R)-yl)-propionic acid methyl ester (2.50 g, 39%) as a colorless oil: [α]23589=−18.62° (c=0.29, chloroform); EI-HRMS m/e calcd for C15H20O3S (M+Na)+ 343.0928, found 343.0927.

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 then quenched with a saturated aqueous ammonium chloride solution (30 mL)
5. concentrationwas then concentrated in vacuo
6. customto remove tetrahydrofuran
7. extractionThe aqueous residue was extracted with ethyl acetate (3×150 mL)
8. dry with materialThe combined organic extracts were dried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo

ORD record

ord-2896110c11844f9fb16b8f60b3c30aab

Source dataset

uspto-grants-2006_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07105671B2