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

HRID 1186288Notes

Reaction equation

HRID 1186288 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].O=[C:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1.N1CCCC1>O>[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:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH:15]=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 71.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A solution of 5-nitro-1H-indole (1 g, 6.17 mmol), tert-butyl 4-oxopiperidine-1-carboxylate (2.458 g, 12.33 mmol) and pyrrolidine (1.530 mL, 18.50 mmol) were refluxed for 48 hours. The reaction was brought to room temperature, diluted with water (50 mL) and product was extracted into ethyl acetate (2×50 mL). The combined ethyl acetate layer was washed with brine (15 mL) and dried (Na2SO4). Solvent was evaporated and crude was diluted with isopropanol: hexanes, 1:6 (20 mL). After stirring for 15 minutes, the solid was filtered off, washed with hexanes (2×10 mL), and dried to obtain tert-butyl 4-(5-nitro-1H-indol-3-yl)-5,6-dihydropyridine-1(2H)-carboxylate (1.515 g, 71.5%). 1H NMR (CDCl3) δ 8.83 (d, 1H, J=1.5 Hz), 8.60 (brs, 1H), 8.14 (dd, 1H, J=2.1, 9.0 Hz), 7.42 (d, 1H, J=9.0 Hz), 7.31 (d, 1H, J=2.1 Hz), 6.21 (s, 1H), 4.20-4.16 (m, 2H), 3.70 (t, 2H, J=5.7 Hz), 2.60-2.50 (m, 2H), 1.51 (s, 9H).

Workup

  1. customwas brought to room temperature
  2. extractionwas extracted into ethyl acetate (2×50 mL)
  3. washThe combined ethyl acetate layer was washed with brine (15 mL)
  4. dry with materialdried (Na2SO4)
  5. customSolvent was evaporated
  6. additioncrude was diluted with isopropanol
  7. filtrationthe solid was filtered off
  8. washwashed with hexanes (2×10 mL)
  9. customdried

Sources & evidence

ORD record
ord-f9963ad60f5b4bc38456d035bd4ede17
Source dataset
uspto-grants-2014_03
Patent number
US08673909B2

Reaction notes

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