Water → 9-[(cyclohexyl)methyl]-5-carbomethoxy-1,2-dihydrocarbazol-4(3H)-one

HRID 567364Notes

Reaction equation

HRID 567364 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([CH2:31]Br)[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1.O>CN(C=O)C.[Na+].[I-]>[CH:25]1([CH2:31][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])[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 137636Cyclohexane, (bromomethyl)-2×HCID 11368514methyl 4-oxo-2,3,4,9-tetrahydro-1H-carbazole-5-carboxylate

Product 1

HCID 227389909-[(cyclohexyl)methyl]-5-carbomethoxy-1,2-dihydrocarbazol-4(3H)-oneYield 97.6%

Reagents, catalysts & solvents 2

HCID 5238Sodium IodideCatalystHCID 6228DimethylformamideSolvent

Procedure

A 0° C. suspension of 5-carbomethoxy-1,2-dihydro-9H-carbazol-4(3H)-one (1.0 g, 4.11 mmol), a catalytic amount of NaI (ca. 10 mg) and K2CO3 (1.1 g, 8.22 mmol) in 10 mL of DMF was treated with cyclohexylmethyl bromide (0.631 mL, 4.52 mmol). After stirring overnight at ambient temperature, an additional 0.63 mL cyclohexylmethylbromide was added, and the resulting mixture was heated at 60° C. for 3 hours. The mixture was poured into H2O (30 mL) and extracted with EtOAc (2×25 mL). The combined organic layers were washed with H2O (4×50 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by radial chromatography on silica gel (elution with a gradient of 20% to 40% EtOAc/hexanes) to afford 1.36 g (4.01 mmol; 97%) of 9-[(cyclohexyl)methyl]-5-carbomethoxy-1,2-dihydrocarbazol-4(3H)-one as a white foam. IR (CHCl3, cm−1) 3011, 2932, 2857, 1725, 1649, 1469, 1446, 1288 and 1120. MS (ES) m/e 340 (M+1), 453 (M+AcO−). FAB HRMS m/e, Calcd for C21H26NO3: 340.1913. Found: 340.1916 (M+1).

Workup

  1. temperaturethe resulting mixture was heated at 60° C. for 3 hours
  2. extractionextracted with EtOAc (2×25 mL)
  3. washThe combined organic layers were washed with H2O (4×50 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by radial chromatography on silica gel (
  8. washelution with a gradient of 20% to 40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-59a8bc6e66bc4eb3abd4430d7c7f9976
Source dataset
uspto-grants-2001_01
Patent number
US06177440B1

Reaction notes

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