반응 #1342887

반응 방정식

sodium borohydride

6-(2-fluoro-3-formyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)-2-methoxynicotinonitrile

Sodium borohydride

HCl

sodium borohydride

→

6-(4-fluoro-1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-5-yloxy)-2-methoxynicotinonitrile

수율 20.1%

용매

methanol

반응 조건

후처리

1. 1
   workup.STIRRINGstirred at room temperature for 2 hours
2. 2
   온도The reaction was cooled again to 0° C. on an ice water bath
3. 3
   workup.STIRRINGThe reaction was stirred at room temperature for 1 hour
4. 4
   온도The reaction was again cooled to 0° C.
5. 5
   workup.STIRRINGThe reaction was stirred at room temperature for one hour
6. 6
   추출The solution was then extracted
7. 7
   세척The organic layer was washed two more times with the 0.5 M boronic acid solution
8. 8
   세척washed with brine
9. 9
   건조dried over anhydrous sodium sulfate
10. 10
    여과filtered
11. 11
    기타The solvent was removed under reduced pressure
12. 12
    기타The residue was purified by silica gel column

실험 절차

A solution of 6-(2-fluoro-3-formyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)-2-methoxynicotinonitrile (1.45 g, 3.64 mmol) in methanol (15 mL) was put on an ice water bath. Sodium borohydride was added in portions. The reaction was stirred at 0° C. for five minutes and then stirred at room temperature for 2 hours. The reaction was cooled again to 0° C. on an ice water bath and sodium borohydride (0.034 g, 0.91 mmol) was added. The reaction was stirred at room temperature for 1 hour. The reaction was again cooled to 0° C. and sodium borohydride (0.034 g, 0.91 mmol) was again added. The reaction was stirred at room temperature for one hour. The reaction was neutralized to pH 6 to 7 using 1 M HCl. The solution was then extracted using ethyl acetate and 0.5 M boronic acid solution in water. The organic layer was washed two more times with the 0.5 M boronic acid solution, then washed with brine, dried over anhydrous sodium sulfate, and filtered. The solvent was removed under reduced pressure. The residue was purified by silica gel column using Combiflash to give 6-(4-fluoro-1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-5-yloxy)-2-methoxynicotinonitrile (0.220 g, 20% yield). ES(−)MS m/z=300 (M−H)−; 1H NMR (400 MHz, DMSO-d6) δ ppm 3.67 (s, 3H), 5.11 (s, 2H), 6.82 (d, J=8.2 Hz, 1H), 7.39 (t, J=6.8, J=7.5 Hz, 1H), 7.60 (d, J=7.8 Hz, 1H), 8.28 (d, J=8.2 Hz, 1H), 9.47 (s, 1H).

출처