반응 #1497517

반응 방정식

BnBr

6-bromo-1H-indazole

NaH

NaH

→

N2-benzyl-6-bromo-2H-indazole

수율 35.0%

N1-Benzyl-6-bromo-1H-indazole

수율 20.0%

용매

THF

THF

반응 조건

후처리

1. 1
   온도was cooled in an ice bath
2. 2
   workup.ADDITIONwas added slowly
3. 3
   기타the cooling bath removed
4. 4
   workup.WAITthe mixture left
5. 5
   workup.WAITAfter a further 1 h at RT
6. 6
   농축1 h at 50° C., the mixture was concentrated
7. 7
   기타chromatographed directly on silica using a 4 cm diameter column with 1:3 EtOAc/cyclohexane as eluent
8. 8
   기타Only partial separation
9. 9
   기타so the mixed fractions were re-purified on an 8 cm diameter column

실험 절차

A suspension of NaH (60 wt % in mineral oil, 5.6 g, 140.0 mmol) in dry THF (150 mL) was cooled in an ice bath, and a suspension of 6-bromo-1H-indazole (27.6 g, 140 mmol) in dry THF (150 mL) was added slowly. The liquid portion became red, but some solids remained. After 30 min, BnBr (17.1 mL, 147.4 mmol) was added, the cooling bath removed, and the mixture left to stir for 3 h at RT. 1H NMR of a sample showed a product ration of 1:1.7 (N1:N2) and incomplete conversion; additional NaH (1.0 g, 25.0 mmol) was added. After a further 1 h at RT and 1 h at 50° C., the mixture was concentrated and chromatographed directly on silica using a 4 cm diameter column with 1:3 EtOAc/cyclohexane as eluent. Only partial separation was achieved, and so the mixed fractions were re-purified on an 8 cm diameter column using approx. 0.5 kg of silica. Samples of both N1-Benzyl-6-bromo-1H-indazole (Rf 0.5, 7.9 g, 20%) and N2-benzyl-6-bromo-2H-indazole (Rf 0.45, 14.2 g, 35%) were isolated, along with some mixed fractions that were retained against future requirements. N1-Benzyl-6-bromo-1H-indazole: 1H NMR (400 MHz, CDCl3) δ 8.00 (d, J=0.6 Hz, 1H), 7.58 (d, J=8.6 Hz, 1H), 7.52 (s, 1H), 7.36-7.20 (m, 4H), 7.20-7.15 (m, 2H), 5.53 (s, 2H). MS (ES+): 287 (79Br, [M+H]+), 289 (81Br, [M+H]+) calcd for [C14H11BrN2+H]+ 287.0 (79Br). N2-benzyl-6-bromo-2H-indazole: 1H NMR (300 MHz, CDCl3) δ 7.92-7.88 (m, 1H), 7.85 (s, 1H), 7.52-7.46 (m, 1H), 7.41-7.32 (m, 3H), 7.31-7.24 (m, 2H), 7.14 (dd, J=8.9, 1.6 Hz, 1H), 5.56 (s, 2H). MS (ES+): 287 (79Br, [M+H]+), 289 (81Br, [M+H]+); calcd for [C14H11BrN2+H]+ 287.0 (79Br).

출처