Hydrochloric Acid → 1-(2-Phenylpyrimidin-5-yl)ethanone

온도

80 °C

A stirring mixture consisting of palladium(II) acetate (215 mg, 0.32 mmol) and triphenylphosphine (335 mg, 1.28 mmol) in 1,4-dioxane (25 mL) was heated at 80° C. for 30 minutes. The dark reaction mixture was cooled to room temperature, and to this reaction mixture was added a solution consisting of 5-bromo-2-phenylpyrimidine (Example 1A, 3.0 g, 13 mmol) and tributyl(1-ethoxyvinyl)tin (4.74 mL, 14.0 mmol) in 1,4-dioxane (63 mL). The reaction mixture was stirred and heated at 75° C. overnight and was subsequently cooled to room temperature. The reaction progress was monitored by thin layer chromatography (95:5 v/v hexanes-ethyl acetate) until completion. The reaction mixture was treated with 1 N hydrochloric acid (19 mL) for one hour at room temperature and poured into a saturated aqueous sodium bicarbonate solution. The organic material was extracted two times with a mixture of ethyl acetate and hexanes, and the combined organic phase was washed sequentially with water and brine, and was dried over anhydrous magnesium sulfate, filtered through a well packed pad of magnesium sulfate, and concentrated under reduced pressure. The residue was dissolved in dichloromethane (30 mL) and diluted with hexanes (30 mL). The resulting precipitate was filtered to give the title intermediate (872 mg). The filtrate was applied to a 80-g silica column eluted with 1:1:9 v/v/v ethyl acetate-dichloromethane-hexanes to afford 1.01 g of additional title intermediate (1.88 g total, 74%); Rf 0.23 with 9:1 v/v hexanes-ethyl acetate solvent system; 1H-NMR (400 MHz; DMSO-d6) δ 9.4 (s, 2H), 8.45-8.50 (m, 2H), 7.5-7.7 (m, 3H), 2.68 (s, 3H); MS (ESI+) m/z 199 (M+1).

1. customThe dark reaction mixture
2. temperaturewas cooled to room temperature
3. additionto this reaction mixture was added a solution
4. temperatureheated at 75° C. overnight
5. temperaturewas subsequently cooled to room temperature
6. extractionThe organic material was extracted two times
7. additionwith a mixture of ethyl acetate and hexanes
8. washthe combined organic phase was washed sequentially with water and brine
9. dry with materialwas dried over anhydrous magnesium sulfate
10. filtrationfiltered through a well packed pad of magnesium sulfate
11. concentrationconcentrated under reduced pressure
12. dissolutionThe residue was dissolved in dichloromethane (30 mL)
13. additiondiluted with hexanes (30 mL)
14. filtrationThe resulting precipitate was filtered

ORD 기록

ord-7990a3e8a27344c2bcf41627619d1d3b

출처 데이터셋

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08536185B2