Sodium Carbonate → (1S,2R)-4'-(2-Hydroxy-1-methyl-4-pyridin-3-yl-butoxy)-2-methyl-biphenyl-4-carbonitrile

온도

100 °C

Prepared according to the method described in Example 12b) from (1S,2R)-4-[2-(tert-butyldimethylsilanyloxy)-1-methyl-4-pyridin-3-ylbutoxy]benzeneboronic acid (0.20 g, Example 11)), 4-bromo-3-methylbenzonitrile (0.20 g), 2M aqueous sodium carbonate solution (0.5 ml) and tetrakis(triphenylphosphine)palladium (0) (0.02 g) in toluene (5 ml) and ethanol (2 ml). The reaction mixture was heated at 100° C. under nitrogen for 4 hours. After cooling, the solution was concentrated under reduced pressure. Concentrated hydrochloric acid (1 ml) was added to a solution of the residue in methanol (5 ml) and the suspension stirred at room temperature for 2 hours. The mixture was concentrated under reduced pressure and the residue partitioned between diethyl ether and water. The aqueous layer was neutralised with a saturated solution of sodium bicarbonate in water and extracted with dichloromethane. The combined organics were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by normal-phase HPLC eluting with a gradient of 0-25% ethanol in dichloromethane to give an oil (0.15 g)

1. customPrepared
2. temperatureAfter cooling
3. concentrationthe solution was concentrated under reduced pressure
4. additionConcentrated hydrochloric acid (1 ml) was added to a solution of the residue in methanol (5 ml)
5. concentrationThe mixture was concentrated under reduced pressure
6. customthe residue partitioned between diethyl ether and water
7. extractionextracted with dichloromethane
8. dry with materialThe combined organics were dried over anhydrous magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customThe residue was purified by normal-phase HPLC
12. washeluting with a gradient of 0-25% ethanol in dichloromethane

ORD 기록

ord-6ab7a22341b0404899a2be9dd2f737aa

출처 데이터셋

uspto-grants-2001_10

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US06300352B1