Cyclobutanone → HCID 89924012, compound

Temperature

-78 °C

5-Bromo-2-iodopyrimidine (12.5 g, 43.88 mmol) was suspended in dry toluene (250 mL), then cooled to −78° C. under N2. n-Butyllithium (2.5M solution in hexanes, 20 mL) was added dropwise, and the reaction mixture was aged for 20 minutes prior to dropwise addition of a solution of cyclobutanone (3.75 g, 53.5 mmol) in dry toluene (10 mL). The reaction mixture was stirred at −78° C. for 45 minutes, then allowed to warm to room temperature. The reaction mixture was diluted with water (100 mL) and extracted with EtOAc (3×300 mL). The combined organic extracts were dried over MgSO4 and the solvent removed under reduced pressure. The resulting brown oil was purified by chromatography on silica (Biotage, 340 g cartridge), eluting with a gradient of 0-100% ethyl acetate in heptanes, to afford the title compound (4.76 g) as a bright yellow solid. δH (500 MHz, CD3OD) 8.80 (s, 2H), 2.57 (dddd, J 11.2, 5.2, 4.4, 2.5 Hz, 2H), 2.32-2.23 (m, 2H), 1.93-1.76 (m, 2H). Method C HPLC-MS: MH+ m/z 230, RT 1.06 minutes.

1. temperatureto warm to room temperature
2. extractionextracted with EtOAc (3×300 mL)
3. dry with materialThe combined organic extracts were dried over MgSO4
4. customthe solvent removed under reduced pressure
5. customThe resulting brown oil was purified by chromatography on silica (Biotage, 340 g cartridge)
6. washeluting with a gradient of 0-100% ethyl acetate in heptanes

ORD record

ord-1152bafe5e974c1992f5dbbbd8252de2

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09309243B2