Sodium Iodide → 9-[(cyclopentyl)methyl]-5-carbomethoxy-1,2-dihydrocarbazol-4(3H)-one

HRID 567369Notes

Reaction equation

HRID 567369 reaction equation
[C:1]([C:5]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:6]=1[C:7]1[C:8](=[O:18])[CH2:9][CH2:10][CH2:11][C:12]=1[NH:13]2)([O:3][CH3:4])=[O:2].C([O-])([O-])=O.[K+].[K+].[CH:25]1([CH2:30]Cl)[CH2:29][CH2:28][CH2:27][CH2:26]1.[Na+].[I-].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.[Na+].[I-].O>[CH:25]1([CH2:30][N:13]2[C:12]3[CH2:11][CH2:10][CH2:9][C:8](=[O:18])[C:7]=3[C:6]3[C:14]2=[CH:15][CH:16]=[CH:17][C:5]=3[C:1]([O:3][CH3:4])=[O:2])[CH2:29][CH2:28][CH2:27][CH2:26]1

Participants

9

Reactant 5

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 11430Potassium CarbonateHCID 11368514methyl 4-oxo-2,3,4,9-tetrahydro-1H-carbazole-5-carboxylateHCID 12815409(Chloromethyl)cyclopentane4×

Product 1

HCID 227386049-[(cyclopentyl)methyl]-5-carbomethoxy-1,2-dihydrocarbazol-4(3H)-oneYield 71%

Reagents, catalysts & solvents 3

HCID 5238Sodium IodideCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A suspension of 5-carbomethoxy-1,2-dihydro-9H-carbazol-4(3H)-one (820 g, 3.37 mmol), a catalytic amount of NaI (ca. 10 mg) and K2CO3 (930 mg, 6.74 mmol) in 6 mL of DMF was treated with cyclopentylmethyl chloride (JOC, 1964, 29, 421-423; 400 mg, 3.37 mmol). After stirring overnight at ambient temperature, an additional 800 mg of cyclopentylmethyl chloride and 1 g of NaI were added, and the resulting mixture was heated at 80° C. overnight. An additional 800 mg of cyclopentylmethyl chloride and 2.2 g of Cs2CO3 were added, and the reaction mixture was heated at 80° C. for 24 h. An additional 1.6 g of cyclopentylmethyl chloride was added, and the reaction mixture was heated at 80° C. for 3 d The mixture was poured into H2O (30 mL) and extracted with EtOAc (3×10 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The residue was purified by radial chromatography on silica gel (elution with gradient of 10% to 40% EtOAc/hexanes) to afford 775 mg (2.38 mmol; 71%) of 9-[(cyclopentyl)methyl]-5-carbomethoxy-1,2-dihydrocarbazol-4(3H)-one as a brown foam. MS (ES) m/e 326 (M+1), 384 (M+AcO−).

Workup

  1. temperaturethe resulting mixture was heated at 80° C. overnight
  2. temperaturethe reaction mixture was heated at 80° C. for 24 h
  3. temperaturethe reaction mixture was heated at 80° C. for 3 d The mixture
  4. extractionextracted with EtOAc (3×10 mL)
  5. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by radial chromatography on silica gel (elution with gradient of 10% to 40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-a83c6ae3f37e4aee96ce9ecde72e7d50
Source dataset
uspto-grants-2001_01
Patent number
US06177440B1

Reaction notes

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