盐酸 → 7-溴-3,4-二氢-1H-吡啶并[4,3-B]吲哚-2(5H)-羧酸叔丁酯

HRID 1020522笔记

反应方程式

HRID 1020522 反应方程式
[Br:1][C:2]1[CH:3]=[C:4]([NH:8]N)[CH:5]=[CH:6][CH:7]=1.[C:10]([N:17]1[CH2:22][CH2:21][C:20](=O)[CH2:19][CH2:18]1)([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11].Cl.CC(OC(OC(OC(C)(C)C)=O)=O)(C)C.C(N(CC)CC)C>C(O)C.CN(C1C=CN=CC=1)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]2[C:19]3[CH2:18][N:17]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:22][CH2:21][C:20]=3[NH:8][C:4]=2[CH:3]=1

参与物

8

反应物 5

HCID 313盐酸HCID 8471三乙胺HCID 337583-溴苯肼HCID 90495二碳酸二叔丁酯HCID 735900N-叔丁氧羰基-4-哌啶酮

产物 1

HCID 579503747-溴-3,4-二氢-1H-吡啶并[4,3-B]吲哚-2(5H)-羧酸叔丁酯收率 42%

试剂、催化剂与溶剂 2

HCID 142844-二甲氨基吡啶(DMAP)催化剂HCID 702乙醇溶剂

实验过程

3-Bromophenylhydrazine (40.0 g, 0.179 mol) and N-Boc-4-oxo-piperidine (35.4 g, 0.179 mol) were dissolved in ethanol (368 mL), and conc. HCl (72 mL) was added. The reaction mixture was then heated to reflux for 18 h, concentrated and basified using 10% NH4OH in methanol (10%, 100 mL). The solvent was removed, and the residue was suspended in CH2Cl2 (1.2 L). Boc2O (39.2 g, 0.179 mol) followed by DMAP (195 mg, 1.6 mmol) and triethylamine (46.4 mL, 0.358 mol) were then added, and the reaction progressed at room temperature for 18 h. The mixture was washed with 0.5 N HCl, and the organic phase was removed, dried over Na2SO4, filtered and concentrated to dryness. The resulting mixture of regioisomers was purified by flash column chromatography (silica gel, hexanes/EtOAc, 100:0 to 80:20 to 50:50 then 25:75) to give the more polar title compound (26.2 g, 42%) as a yellow solid: 1H NMR (300 MHz, CDCl3) δ 8.16 (br s, 1H), 7.42 (s, 1H), 7.28 (d, J=8.1 Hz, 1H, partially masked by solvent), 7.18 (d, J=8.1 Hz, 1H), 4.60 (s, 2H), 3.80 (t, J=5.5 Hz, 2H), 2.79 (t, J=5.6 Hz, 2H), 1.51 (s, 9H).

后处理

  1. temperatureThe reaction mixture was then heated
  2. temperatureto reflux for 18 h
  3. concentrationconcentrated
  4. customThe solvent was removed
  5. additionwere then added
  6. washThe mixture was washed with 0.5 N HCl
  7. customthe organic phase was removed
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated to dryness
  11. additionThe resulting mixture of regioisomers
  12. customwas purified by flash column chromatography (silica gel, hexanes/EtOAc, 100:0 to 80:20 to 50:50

来源与证据

ORD记录
ord-5b620c905833412783bb4750881d852f
来源数据集
uspto-grants-2014_05
专利号
US08716308B2

反应笔记

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