1,3-Diethyl 2-(3-oxocyclohexyl)propanedioate → 5-bromo-2-(1,3-diethoxy-1,3-dioxopropan-2-yl)-6-fluoro-2,3,4,9-tetrahydro-1H-carbazole-8-carboxylic acid

HRID 523280

Reaction equation

HRID 523280 reaction equation
O=[C:2]1[CH2:7][CH2:6][CH2:5][CH:4]([CH:8]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:3]1.Cl.[Br:20][C:21]1[C:29]([F:30])=[CH:28][C:24]([C:25]([OH:27])=[O:26])=[C:23]([NH:31]N)[CH:22]=1>C(O)(=O)C>[Br:20][C:21]1[C:29]([F:30])=[CH:28][C:24]([C:25]([OH:27])=[O:26])=[C:23]2[C:22]=1[C:7]1[CH2:6][CH2:5][CH:4]([CH:8]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:3][C:2]=1[NH:31]2

Participants

4

Reactant 2

HCID 3170491,3-Diethyl 2-(3-oxocyclohexyl)propanedioateHCID 768481964-Bromo-5-fluoro-2-hydrazinylbenzoic acid hydrochloride2×

Product 1

HCID 1177610905-bromo-2-(1,3-diethoxy-1,3-dioxopropan-2-yl)-6-fluoro-2,3,4,9-tetrahydro-1H-carbazole-8-carboxylic acidYield 49%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A solution of diethyl 2-(3-oxocyclohexyl)malonate (15.26 g, 59.5 mmol) and 4-bromo-5-fluoro-2-hydrazinylbenzoic acid hydrochloride [Intermediate 24B] (17.0 g, 59.5 mmol) in acetic acid (120 mL) was heated at reflux for 2 h, then was stirred overnight at room temperature. The precipitate which formed was collected by filtration to provide a white solid. The filtrate was concentrated and purified by column chromatography on silica gel (80 g), eluting with EtOAc-hexanes (gradient from 0-100%). The resulting oily product was crystallized from a mixture of EtOAc, ether and hexanes to provide additional solid, which was combined with the first solid to provide 5-bromo-2-(1,3-diethoxy-1,3-dioxopropan-2-yl)-6-fluoro-2,3,4,9-tetrahydro-1H-carbazole-8-carboxylic acid as a white solid (10.5 g, 49% yield). Mass spectrum m/z 470, 472 (M+H)+.

Workup

  1. temperatureat reflux for 2 h
  2. customThe precipitate which formed
  3. filtrationwas collected by filtration
  4. customto provide a white solid
  5. concentrationThe filtrate was concentrated
  6. custompurified by column chromatography on silica gel (80 g)
  7. washeluting with EtOAc-hexanes (gradient from 0-100%)
  8. customThe resulting oily product was crystallized from a mixture of EtOAc, ether and hexanes
  9. customto provide additional solid, which

Sources & evidence

ORD record
ord-9d6c9d1b33d246e588d4c05344625996
Source dataset
uspto-grants-2016_05
Patent number
US09334290B2

Linked notes

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