Water → HCID 89923708, compound

Temperature

-78 °C

Ethyl 2-(5-bromopyrimidin-2-yl)acetate (500 mg, 2.04 mmol) was dissolved in THF (8 mL) and the mixture was cooled to −78° C. under nitrogen. LDA in THF/heptane/ethylbenzene (2M, 1.25 mL) was added dropwise, then the mixture was stirred for 15 minutes. Iodomethane (0.22 mL, 3.53 mmol) was added, then the reaction mixture was warmed to room temperature and stirred for a further 2 h. Water (10 mL) was added and the mixture was extracted with ethyl acetate (20 mL). The aqueous layer was acidified to pH ˜5 with 1M HCl, then extracted with additional ethyl acetate (2×20 mL). The combined organic layers were dried over Na2SO4 and concentrated under vacuum. The residue was purified by silica gel chromatography, eluting with a gradient of 0-50% ethyl acetate in heptane, to afford the title compound (417 mg, 79%) as a yellow oil. δH (500 MHz, CDCl3) 8.75 (s, 2H), 4.18 (m, 2H), 4.08 (q, J 7.2 Hz, 1H), 1.60 (d, J 7.3 Hz, 3H), 1.22 (t, J 7.1 Hz, 3H).

1. temperaturethe reaction mixture was warmed to room temperature
2. stirringstirred for a further 2 h
3. extractionthe mixture was extracted with ethyl acetate (20 mL)
4. extractionextracted with additional ethyl acetate (2×20 mL)
5. dry with materialThe combined organic layers were dried over Na2SO4
6. concentrationconcentrated under vacuum
7. customThe residue was purified by silica gel chromatography
8. washeluting with a gradient of 0-50% ethyl acetate in heptane

ORD record

ord-2b03993a25ca47f89ccc122d705bb298

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09309243B2