Sodium hydride → 9-Oxo-6,7,8,9-tetrahydro-pyrido[1,2-a]indole-3-carboxylic acid

HRID 1710454Notes

Reaction equation

HRID 1710454 reaction equation
[H-].[Na+].C(O[C:6]([C:8]1[NH:9][C:10]2[C:15]([CH:16]=1)=[CH:14][CH:13]=[C:12]([C:17]([O:19]CC)=[O:18])[CH:11]=2)=[O:7])C.Br[CH2:23][CH2:24][CH2:25]C(OCC)=O>CN(C=O)C>[O:7]=[C:6]1[C:8]2=[CH:16][C:15]3[C:10]([N:9]2[CH2:25][CH2:24][CH2:23]1)=[CH:11][C:12]([C:17]([OH:19])=[O:18])=[CH:13][CH:14]=3

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 76300Ethyl 4-bromobutyrateHCID 44754779Diethyl 1H-indole-2,6-dicarboxylate

Product 1

HCID 587675619-Oxo-6,7,8,9-tetrahydro-pyrido[1,2-a]indole-3-carboxylic acidYield 95%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a stirred suspension of NaH (260 mg of 60 wt % in mineral oil, 6.50 mmol) in DMF (5 mL) under an atmosphere of dry nitrogen was added 1H-indole-2,6-dicarboxylic acid diethyl ester (see Example 1) (1.50 g, 5.74 mmol) in DMF (40 mL) over 5 min. Ethyl 4-bromobutyrate (1.40 g, 7.2 mmol) was added dropwise, and the reaction was stirred at room temperature for 20 h. The reaction was quenched with water and extracted into methylene chloride (3×50 mL). The combined organic extracts were washed with brine, dried over MgSO4, and concentrated. The crude tri-ester intermediate was taken up in dry THF (30 mL) and to this solution was added potassium tert-butoxide (20 mL of a 1.0 M solution in THF, 20 mmol). After stirring at room temperature for 16 h, the reaction was quenched with water (60 mL) and concentrated HCl (75 mL) and refluxed for 5 h. The resulting suspension was cooled, filtered, then washed with water followed by hexanes. The resulting solid was dried in a vacuum oven to give 9-oxo-6,7,8,9-tetrahydro-pyrido[1,2-a]indole-3-carboxylic acid (1.25 g, 95%) as an analytically pure purple powder.

Workup

  1. customThe reaction was quenched with water
  2. extractionextracted into methylene chloride (3×50 mL)
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. additionwas added potassium tert-butoxide (20 mL of a 1.0 M solution in THF, 20 mmol)
  7. stirringAfter stirring at room temperature for 16 h
  8. customthe reaction was quenched with water (60 mL) and concentrated HCl (75 mL)
  9. temperaturerefluxed for 5 h
  10. temperatureThe resulting suspension was cooled
  11. filtrationfiltered
  12. washwashed with water
  13. customThe resulting solid was dried in a vacuum oven

Sources & evidence

ORD record
ord-0baa09a972ed4550b16ea630d8f8c1a0
Source dataset
uspto-grants-2010_09
Patent number
US07790712B2

Reaction notes

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