Sodium Carbonate → (1S,2R)-2-[4'-(2-Hydroxy-1-methyl-4-pyridin-3-ylbutoxy)biphenyl-4-yl]-N-methylacetamide

온도

110 °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)), 2-(3-bromophenyl)-N-methyl-acetamide (0.244 g, Example 24a)), 2M aqueous sodium carbonate (0.265 ml) and tetrakis(triphenylphosphine)palladium (0) (0.1 g) in toluene (5 ml) and ethanol (2 ml). The reaction was heated at 110° C. for 6 hours. After cooling, the solution was concentrated under reduced pressure the residue was dissolved in methanol (10 ml), concentrated hydrochloric acid (1 ml) was added and the solution stirred at room temperature for 18 hours. The mixture was concentrated under reduced pressure the residue was neutralised using saturated sodium hydrogen carbonate and extracted with ethyl acetate. The combined extracts 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 0-10% ethanol in dichloromethane to give the title compound as an oil which was converted to the oxalic acid salt by treatment with a saturated ethereal solution of oxalic acid to give the title compound as a gum (0.123 g).

1. customPrepared
2. temperatureAfter cooling
3. concentrationthe solution was concentrated under reduced pressure the residue
4. dissolutionwas dissolved in methanol (10 ml)
5. additionconcentrated hydrochloric acid (1 ml) was added
6. concentrationThe mixture was concentrated under reduced pressure the residue
7. extractionextracted with ethyl acetate
8. dry with materialThe combined extracts 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 0-10% ethanol in dichloromethane

ORD 기록

ord-e8910b04050d4fc19ba947fab5b9922f

출처 데이터셋

uspto-grants-2001_10

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US06300352B1