Methyl iodide → Ethyl 2-(4-chloropyrimidin-5-yl)propanoate

Temperature

-20 °C

To a stirred, cooled (−78° C. solution of 5.8 g (29 mmol) of ethyl (4-chloro-5-pyrimidinyl)acetate (see i-48, Step A) in 75 mL of anhydrous THF under an atmosphere of nitrogen was added 15.2 mL (30.4 mmol) of a 2.0 M solution of lithium diisopropylamide in anhydrous THF. The resulting mixture was stirred for 15 min then 2.26 mL (36.1 mmol) of iodomethane was added over 5 min. The reaction mixture was stirred for 15 min, allowed to warm to −20° C. over 45 min, then warmed to 0° C. for 15 min. The reaction mixture was then quenched with a saturated ammonium chloride solution and extracted with 50 mL of dichloromethane. The organic layer was dried over magnesium sulfate, filtered, and evaporated in vacuo. The crude residue was purified by silica gel chromatography eluting with a 20% ethyl acetate in hexanes mixture to afford the title compound (1.9 g, 31%). 1H-NMR (500 MHz, CD3OD) δ: 8.88 (s 1H), 8.74 (s, 1H), 4.17 (m, 2H), 1.58 (d, J=7 Hz, 3H), 1.29 (t, J=7 Hz, 3H). LC-MS: m/z (E/S) 215 (MH)+.

1. stirringThe reaction mixture was stirred for 15 min
2. temperaturewarmed to 0° C. for 15 min
3. customThe reaction mixture was then quenched with a saturated ammonium chloride solution
4. extractionextracted with 50 mL of dichloromethane
5. dry with materialThe organic layer was dried over magnesium sulfate
6. filtrationfiltered
7. customevaporated in vacuo
8. customThe crude residue was purified by silica gel chromatography
9. washeluting with a 20% ethyl acetate in hexanes mixture

ORD record

ord-5bbf82dcb8dc4fc2850b321df6ad3855

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08399480B2