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

HRID 1419175Notes

Reaction equation

HRID 1419175 reaction equation
[Na].[N+:2]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][CH:9]=[CH:8]2)([O-:4])=[O:3].[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][C:24](=O)[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15]>CO>[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][C:24]([C:8]2[C:7]3[C:11](=[CH:12][CH:13]=[C:5]([N+:2]([O-:4])=[O:3])[CH:6]=3)[NH:10][CH:9]=2)=[CH:23][CH2:22]1)=[O:20])([CH3:17])([CH3:15])[CH3:16]

Participants

5

Reactant 3

HCID 225235-NitroindoleHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5360545Sodium

Product 1

HCID 54262828tert-Butyl 4-(5-nitro-1H-indol-3-yl)-5,6-dihydropyridine-1(2H)-carboxylateYield 72%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
65 °C

Procedure

To a stirred solution of sodium (2.51 g, 105 mmol, 7 eq) in absolute methanol (50 mL) was added 5-nitroindole (2.43 g, 15.0 mmol) and N-t-butoxycarbonyl4-piperidone (8.96 g, 45.0 mmol, 3.0 eq). The resulting reaction solution was heated at reflux (65° C.) under nitrogen for 24 hours. The resulting reaction solution was evaporated under reduced pressure, and the residue was partitioned between a saturated solution of sodium hydrogen carbonate (50 mL) and ethyl acetate (50 mL). The organic layer was removed, and the aqueous layer was extracted with ethyl acetate (2×50 mL). The organic extracts were combined, dried (MgSO4), and evaporated under reduced pressure. Column chromatography of the extraction residue using silica gel (approximately 100 g) and elution with ethyl acetate in hexanes [1:2 to 1:1 gradient] afforded the title compound (72%) as yellow solid: mp, decomposes 230° C.; 1H NMR (CDCl3) δ 9.24 (br s, 1H), 8.78 (d, J=1.3 Hz, 1H), 8.09 (dd, J=1.4 and 9.4 Hz, 1H), 7.40 (d, J=9.3 Hz, 1H), 7.30 (d, J=1.8 Hz, 1H), 6.17-6.15 (m, 1H), 4.16-4.13 (m, 2H), 3.68 (t, J=5.8 Hz, 2H), 2.58-2.48 (m, 2H), 1.50 (s, 9H); Anal. calcd for C15H21N3O4.0.1 H2O: C, 62.63; H, 6.19; N, 12.17. Found: C, 62.71; H, 6.09; N, 11.81.

Workup

  1. customThe resulting reaction solution
  2. temperaturewas heated
  3. customThe resulting reaction solution
  4. customwas evaporated under reduced pressure
  5. customthe residue was partitioned between a saturated solution of sodium hydrogen carbonate (50 mL) and ethyl acetate (50 mL)
  6. customThe organic layer was removed
  7. extractionthe aqueous layer was extracted with ethyl acetate (2×50 mL)
  8. dry with materialdried (MgSO4)
  9. customevaporated under reduced pressure
  10. washsilica gel (approximately 100 g) and elution with ethyl acetate in hexanes [1:2 to 1:1 gradient]

Sources & evidence

ORD record
ord-23b001ac4e774e748feeaa874fe8168b
Source dataset
uspto-grants-1999_03
Patent number
US05886008

Reaction notes

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