반응 #339672

반응 방정식

acetone dry ice

1-butyl-6-methoxy-1H-indole-3-carbonitrile

Trimethyl borate

4-iodoaniline

n-BuLi

(i-Pr)2NH

→

2-(4-aminophenyl)-1-butyl-6-methoxy-1H-indole-3-carbonitrile

수율 86.0%

용매

DMF

THF

THF

반응 조건

후처리

1. 1
   workup.ADDITIONis added dropwise
2. 2
   workup.STIRRINGThis solution is stirred for 15 min at −78° C.
3. 3
   workup.WAITfollowing by 20 min at −20° C
4. 4
   workup.STIRRINGthe reaction mixture is stirred for 15 min at −20° C. after which the cooling bath
5. 5
   기타is removed
6. 6
   workup.STIRRINGthis solution is stirred further at room temperature for 1 h
7. 7
   workup.ADDITIONA solution of K3PO4 is added (11.7 mL, 3M aqueous solution, 35.1 mmol)
8. 8
   세척a 5 mL rinse)
9. 9
   workup.STIRRINGThe reaction mixture is stirred overnight (ca. 18 h)
10. 10
    workup.ADDITIONwater (80 mL) is added
11. 11
    추출the product is extracted with EtOAc (3×50 mL)
12. 12
    건조The combined organic fractions are dried over MgSO4
13. 13
    여과filtered
14. 14
    농축concentrated under reduced pressure
15. 15
    기타The crude product is purified
16. 16
    기타via flush chromatography on silica gel (5-60% EtOAc/Hexanes as eluant)

실험 절차

To a solution of (i-Pr)2NH (1.35 mL, 9.65 mmol) in THF (30 mL) cooled to −78° C. is added n-BuLi (3.7 mL, 2.5M in hexanes, 9.21 mmol) in one portion. The acetone/dry ice bath is exchanged for ice/water bath and the solution is stirred further for 40 min. The solution is cooled to −78° C. and solution of 1-butyl-6-methoxy-1H-indole-3-carbonitrile, prepared as in example 1A (2.0 g, 8.77 mmol) in THF (10 mL) is added dropwise. This solution is stirred for 15 min at −78° C., following by 20 min at −20° C. Trimethyl borate (1.0 mL, 8.77 mmol) is added, the reaction mixture is stirred for 15 min at −20° C. after which the cooling bath is removed and this solution is stirred further at room temperature for 1 h. A solution of K3PO4 is added (11.7 mL, 3M aqueous solution, 35.1 mmol) followed by a solution of 4-iodoaniline (2.5 g, 11.40 mmol) and PdCl2dppf catalyst (640 mg, 0.88 mmol) in DMF (40 mL, plus a 5 mL rinse). The reaction mixture is stirred overnight (ca. 18 h) and then water (80 mL) is added and the product is extracted with EtOAc (3×50 mL). The combined organic fractions are dried over MgSO4, filtered and concentrated under reduced pressure. The crude product is purified via flush chromatography on silica gel (5-60% EtOAc/Hexanes as eluant) to afford the desired 2-(4-aminophenyl)-1-butyl-6-methoxy-1H-indole-3-carbonitrile as a tan solid (2.4 g, 86% yield).

출처