Diisopropylamine → HCID 67482160, compound

Temperature

-78 °C

A solution of diisopropylamine (0.67 mL, 4.82 mmol) in tetrahydrofuran (30 mL) cooled to −78° C. under an argon atmosphere was treated with a 2.5M solution of n-butyllithium in hexanes (1.93 mL, 4.82 mmol). The reaction mixture was stirred at −78° C. for 15 min. At this time, the reaction was treated with a solution of (4-methanesulfonyl-phenyl)-acetic acid methyl ester (1.00 g, 4.38 mmol) in tetrahydrofuran (6 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (2 mL). The bright yellow solution was allowed to stir at −78° C. for 1 h, after which time, a solution of 2-bromomethyl-tetrahydro-pyran (0.67 mL, 5.26 mmol) in 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (1 mL) was added via a cannula. The reaction mixture was then allowed to warm to 25° C., where it was stirred for 16 h. The reaction mixture was then quenched by the addition of a saturated aqueous ammonium chloride solution (20 mL) and extracted with ethyl acetate (3×15 mL). The organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 70/30 hexanes/ethyl acetate) afforded 2-(4-methanesulfonyl-phenyl)-3-(tetrahydro-pyran-2-yl)-propionic acid methyl ester (157 mg, 11%) as a colorless oil: EI-HRMS m/e calcd for C16H22O5S (M+) 326.1188, found 326.1189.

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 by the addition of a saturated aqueous ammonium chloride solution (20 mL)
5. extractionextracted with ethyl acetate (3×15 mL)
6. dry with materialThe organic layers were dried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo

ORD record

ord-3fd216b715be485c90dc0bf0a952b5f1

Source dataset

uspto-grants-2006_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07105671B2