Triethylamine → 1,3-dihydro-1-(4-morpholinyl)-3-(4-pyridinylmethyl)-2H-indol-2-one

HRID 440444Notes

Reaction equation

HRID 440444 reaction equation
[N:1]1([N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH2:9][C:8]2=[O:16])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C(N(CC)CC)C.[N:24]1[CH:29]=[CH:28][C:27]([CH:30]=O)=[CH:26][CH:25]=1>CO>[N:1]1([N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH:9]([CH2:30][C:27]3[CH:28]=[CH:29][N:24]=[CH:25][CH:26]=3)[C:8]2=[O:16])[CH2:2][CH2:3][O:4][CH2:5][CH2:6]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 133894-PyridinecarboxaldehydeHCID 152843961,3-dihydro-1-(4-morpholinyl)-2H-indol-2-one

Product 1

HCID 233539761,3-dihydro-1-(4-morpholinyl)-3-(4-pyridinylmethyl)-2H-indol-2-oneYield 60.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 1,3-dihydro-1-(4-morpholinyl)-2H-indol-2-one (301 mg, 1.38 mmole), triethylamine (0.22 ml, 1.52 mmole), 4-pyridinecarboxaldehyde (0.15 ml, 1.52 mmole) in methanol (3 ml) was refluxed for 30 minutes. The volatiles were evaporated and the crude product was partitioned between water and dichloromethane. The organic layer was washed with brine, dried over magnesium sulfate, filtered and concentrated. The crude red oil was characterized by mass spec., m/e 308 (M+H, 100%) for the aldol/dehydration product. The crude material was immediately dissolved in methanol (10 ml), cooled to 0° C., to which was added sodium borohydride (168 mg). After stirring 30 minutes, normal extractive workup afforded a yellow foam, which was purified by column chromatography using 5% methanol-chloroform. The product was recrystallized from hexane-ethyl acetate to give 259 mg of a powder, m.p. 108°-110° C. Anal (C18H19N3O2): C,H,N.

Workup

  1. temperaturewas refluxed for 30 minutes
  2. customThe volatiles were evaporated
  3. customthe crude product was partitioned between water and dichloromethane
  4. washThe organic layer was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. dissolutionThe crude material was immediately dissolved in methanol (10 ml)
  9. additionwas added sodium borohydride (168 mg)
  10. customnormal extractive workup afforded a yellow foam, which
  11. customwas purified by column chromatography
  12. customThe product was recrystallized from hexane-ethyl acetate

Sources & evidence

ORD record
ord-b2e08d39c1f040ccbfb2041d0daf6dc3
Source dataset
uspto-grants-1996_05
Patent number
US05519132

Reaction notes

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