Ethyl 4-oxocyclohexanecarboxylate → 6-bromo-3-(ethoxycarbonyl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxylic acid

HRID 2410655Notes

Reaction equation

HRID 2410655 reaction equation
Cl.Cl.[Br:3][C:4]1[CH:5]=[CH:6][C:7]([NH:13]N)=[C:8]([CH:12]=1)[C:9]([OH:11])=[O:10].O=[C:16]1[CH2:21][CH2:20][CH:19]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:18][CH2:17]1.CCCCCC.C(OCC)(=O)C>CC(O)=O.C(OCC)(=O)C.CCOCC>[Br:3][C:4]1[CH:5]=[C:6]2[C:7](=[C:8]([C:9]([OH:11])=[O:10])[CH:12]=1)[NH:13][C:16]1[CH2:21][CH2:20][CH:19]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:18][C:17]2=1

Participants

7

Reactant 3

HCID 317638Ethyl 4-oxocyclohexanecarboxylateHCID 21226206Ethyl acetate hexaneHCID 666052955-Bromo-2-hydrazinylbenzoic acid dihydrochloride

Product 1

HCID 666044176-bromo-3-(ethoxycarbonyl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxylic acidYield 56.6%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred suspension of 5-bromo-2-hydrazinylbenzoic acid dihydrochloride (3.08 g, 10.13 mmol) in AcOH, (˜0.5M) (20 mL) was added ethyl 4-oxocyclohexanecarboxylate (1.759 g, 10.34 mmol) at room temperature. The cream-colored reaction mixture was then stirred under reflux for 4 h. The reaction mixture was cooled to room temperature and concentrated in vacuo to afford a yellow solid. The solid was then dissolved in ethyl acetate, washed with 1N aqueous HCl and brine solution. The organic phase was dried over Na2SO4 and concentrated to give the crude product, which was then suspended in ether and the yellow solid was collected by filtration, air-dried. Additional quantity was obtained by combining the filtrate followed by silica gel column chromatography (hexane/ethyl acetate=50/50-0/100) to give 2.1 g of 6-bromo-3-(ethoxycarbonyl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxylic acid. MS (ESI) m/z 367.2 (M+H). 1H NMR (DMSO-d6) δ ppm 13.2 (br s, 1H), 10.8 (s, 1H), 7.8 (s, 1H), 7.6 (s, 1H), 3.92 (m, 4H), 3.77 (q, 2H, J=7.8 Hz), 2.52-2.81 (m, 7H), 1.3 (t, 3H).

Workup

  1. temperatureunder reflux for 4 h
  2. concentrationconcentrated in vacuo
  3. customto afford a yellow solid
  4. washwashed with 1N aqueous HCl and brine solution
  5. dry with materialThe organic phase was dried over Na2SO4
  6. concentrationconcentrated
  7. customto give the crude product, which
  8. filtrationthe yellow solid was collected by filtration
  9. customair-dried
  10. customAdditional quantity was obtained

Sources & evidence

ORD record
ord-1d67c5778eca440d99e449fd74154b57
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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