تفاعل #48807

معادلة التفاعل

3-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethyloxy)-5-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)benzamide

3-fluoro-4-methoxyphenylboronic acid

triethylamine

→

desired compound

المردود 30.9%

3-(3-Fluoro-4-methoxyphenoxy)-5-[(1S)-2-hydroxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide

المردود 30.9%

المذيبات

DCM

ظروف التفاعل

المعالجة

1. 1
   ترشيحThe reaction mixture was filtered through celite
2. 2
   غسيلwashed with DCM (2×10 mL)
3. 3
   أخرىthe DCM removed in vacuo
4. 4
   أخرىThe residue was partitioned between ethyl acetate
5. 5
   غسيلa saturated solution of sodium bicarbonate, the organic layer washed with brine
6. 6
   تجفيفdried (MgSO4)
7. 7
   تركيزconcentrated in vacuo
8. 8
   workup.ADDITION3.5M Hydrochloric acid (0.5 mL) was added to a solution of the residual oil
9. 9
   workup.DISSOLUTIONdissolved in methanol (5 mL)
10. 10
    workup.ADDITIONThe reaction mixture was diluted with water (10 mL)
11. 11
    استخلاصextracted with ethyl acetate (20 mL)
12. 12
    غسيلThe organic layer was washed with brine
13. 13
    تجفيفdried (MgSO4)
14. 14
    تركيزconcentrated in vacuo
15. 15
    أخرىThe residue was chromatographed on silica
16. 16
    غسيلeluting with ethyl acetate

الإجراء التجريبي

A solution of 3-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethyloxy)-5-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)benzamide (0.30 g, 0.74 mmol), 3-fluoro-4-methoxyphenylboronic acid (255 mg, 1.5 mmol), copper (II) acetate (0.202 g, 1.11 mmol), triethylamine (0.517 mL, 3.71 mmol) and freshly activated 4 Å molecular sieves (1 g) in DCM (40 mL) was stirred at ambient temperature and under ambient atmosphere for 2 days. The reaction mixture was filtered through celite, washed with DCM (2×10 mL), the DCM removed in vacuo. The residue was partitioned between ethyl acetate and a saturated solution of sodium bicarbonate, the organic layer washed with brine, dried (MgSO4) and concentrated in vacuo. 3.5M Hydrochloric acid (0.5 mL) was added to a solution of the residual oil dissolved in methanol (5 mL) and stirred at RT for 20 minutes, then the solution neutralised with saturated sodium bicarbonate. The reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate (20 mL). The organic layer was washed with brine, dried (MgSO4), and concentrated in vacuo. The residue was chromatographed on silica, eluting with ethyl acetate, to give the desired compound (95 mg).

المصدر