5-Nitroindole → tert-Butyl 4-(5-nitro-1H-indol-3-yl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 2043508Notes

Reaction equation

HRID 2043508 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[CH:7]2)([O-:3])=[O:2].N1CCCC1.[C:18]([N:25]1[CH2:30][CH2:29][C:28](=O)[CH2:27][CH2:26]1)([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19]>C(O)C>[N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[C:7]2[C:28]1[CH2:29][CH2:30][N:25]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:26][CH:27]=1)([O-:3])=[O:2]

Participants

5

Reactant 3

HCID 225235-NitroindoleHCID 31268PyrrolidineHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate

Product 1

HCID 54262828tert-Butyl 4-(5-nitro-1H-indol-3-yl)-5,6-dihydropyridine-1(2H)-carboxylateYield 99.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 5-nitroindole (38) (2.0 g, 12.334 mmol) in dry ethanol (20 mL) was treated with pyrrolidine (3.08 mL, 37.002 mmol) followed by N-Boc-4-piperidone (4.91 g, 24.668 mmol) at room temperature and the resulting solution was refluxed for 3 days. The reaction was brought to room temperature, the solvent was evaporated and the crude product was purified by column chromatography (ethyl acetate:hexanes, 1:3) to obtain compound 85 (4.2 g, quantitative) as a solid. mp 210-212° C.; 1H NMR (DMSO-d6) δ 1.36-1.43 (m, 11H), 3.57 (t, 2H, J=5.7 Hz), 4.08 (s, 2H), 6.20 (s, 1H), 7.56 (d, 1H, J=9.0 Hz), 7.71 (s, 1H), 8.02 (dd, 1H, J=2.1, 9.0 Hz), 8.71 (d, 1H, J=2.1, Hz), 11.93 (s, 1H); ESI-MS m/z (%): 366 (M.Na+, 100), 288 (52).

Workup

  1. temperaturethe resulting solution was refluxed for 3 days
  2. customwas brought to room temperature
  3. customthe solvent was evaporated
  4. customthe crude product was purified by column chromatography (ethyl acetate:hexanes, 1:3)

Sources & evidence

ORD record
ord-8a837b0399c44f4c997b70459bb282fd
Source dataset
uspto-grants-2013_11
Patent number
US08586620B2

Reaction notes

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