Acetaldehyde → HCID 18353311, compound

To a stirred solution of borane dimethyl sulphide complex (1.42 ml, 15 mmol) in THF at 0° was added dropwise α-pinene (5 ml, 31.5 mmol). The reaction mixture was stirred at room temperature for 30 min. The reaction mixture was cooled to −35° and ethyl propionate (1.47 g, 1.52 ml, 15 mmol) added dropwise. The reaction mixture was stirred at room temperature for 2 h and then cooled to 0°. Acetaldehyde (5 ml, 3.94 g, 89 mmol) was added dropwise. The reaction mixture was heated to reflux for 1 h. Upon cooling the solvent and volatiles were removed by evaporation in vacuo. The residue was dissolved in THF (50 ml) and pinacol (1.8 g, 18 mmol) added. The reaction mixture was stirred for 1 h at room temperature. The solvent and volatiles were removed by evaporation in vacuo. To the crude product was added 2,4-dichloropyrimidine (2.24 g, 15 mmol) followed by cesium fluoride (4.56 g, 30 mmol) and tetrakis(triphenylphosphine)palladium (0) (0.88 g, 0.75 mmol). The reaction mixture was diluted with dioxane (50 ml) and heated under reflux for 3 h. Upon cooling the reaction mixture was poured into saturated sodium hydrogen carbonate solution (100 ml) and extracted twice with dichloromethane (100 ml). The combined organic fractions were dried over magnesium sulphate, filtered and the solvent removed by evaporation in vacuo. Purification by flash column chromatography (diisopropylethersilica) gave the title compound (1.59 g, 50%). 1H NMR (CDCl3) δ 6.78 (1H, d, J 12 Hz), 6.62 (1H, d, J 12 Hz), 4.22 (2H, q, J 8 Hz) and 1.21 (3H, t, J 8 Hz).

1. temperatureThe reaction mixture was cooled to −35°
2. stirringThe reaction mixture was stirred at room temperature for 2 h
3. temperaturecooled to 0°
4. temperatureThe reaction mixture was heated
5. temperatureto reflux for 1 h
6. temperatureUpon cooling the solvent and volatiles
7. customwere removed by evaporation in vacuo
8. dissolutionThe residue was dissolved in THF (50 ml)
9. stirringThe reaction mixture was stirred for 1 h at room temperature
10. customThe solvent and volatiles were removed by evaporation in vacuo
11. temperatureheated
12. temperatureunder reflux for 3 h
13. temperatureUpon cooling the reaction mixture
14. extractionextracted twice with dichloromethane (100 ml)
15. dry with materialThe combined organic fractions were dried over magnesium sulphate
16. filtrationfiltered
17. customthe solvent removed by evaporation in vacuo
18. customPurification by flash column chromatography (diisopropylethersilica)

ORD record

ord-8c9485d9c057449990f0edd8a1f2b29e

Source dataset

uspto-grants-2001_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06319922B1