tert-Butyl 4-oxopiperidine-1-carboxylate → 1,1-dimethylethyl 4-[7-(aminocarbonyl)-5-bromo-1H-indol-3-yl]-3,6-dihydro-1(2H)-pyridinecarboxylate

HRID 1806200Notes

Reaction equation

HRID 1806200 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=1)[NH:7][CH:6]=[CH:5]2.O=[C:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]1.C[O-].[Na+]>CO>[NH2:13][C:11]([C:9]1[CH:10]=[C:2]([Br:1])[CH:3]=[C:4]2[C:8]=1[NH:7][CH:6]=[C:5]2[C:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH:16]=1)=[O:12]

Participants

5

Reactant 3

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 10942334Sodium MethoxideHCID 596006575-bromo-1H-indole-7-carboxamide

Product 1

HCID 596006561,1-dimethylethyl 4-[7-(aminocarbonyl)-5-bromo-1H-indol-3-yl]-3,6-dihydro-1(2H)-pyridinecarboxylateYield 514.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 5-bromo-1H-indole-7-carboxamide (10 g, 41.84 mmol) in methanol (5 mL), 1,1-dimethylethyl 4-oxo-1-piperidinecarboxylate (684 mg, 3.42 mmol) and sodium methoxide (0.5 M in THF, 13.7 mL, 6.84 mmol) were added. The reaction mixture was stirred at reflux temperature for 16 hours. All solvent was evaporated under reduced pressure. The residue was partitioned between ethyl acetate (100 mL) and water (100 mL). The combined organic phase was dried over MgSO4 and concentrated under reduced pressure, and purified by flash column chromatography (ethyl acetate/hexanes, 1/1) to give the desired product (7.4 g, 43%).

Workup

  1. temperatureat reflux temperature for 16 hours
  2. customAll solvent was evaporated under reduced pressure
  3. customThe residue was partitioned between ethyl acetate (100 mL) and water (100 mL)
  4. dry with materialThe combined organic phase was dried over MgSO4
  5. concentrationconcentrated under reduced pressure
  6. custompurified by flash column chromatography (ethyl acetate/hexanes, 1/1)

Sources & evidence

ORD record
ord-c70a59257e6c46828ef63950411f96dd
Source dataset
uspto-grants-2013_01
Patent number
US08354406B2

Reaction notes

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