Hydrochloric Acid → 9-[(2,3-Difluorophenyl)methyl]-4-hydroxy-5-carbamoyl carbazole

HRID 567329Notes

Reaction equation

HRID 567329 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][N:10]1[C:22]2[CH:21]=[CH:20][CH:19]=[C:18]([OH:23])[C:17]=2[C:16]2[C:11]1=[CH:12][CH:13]=[CH:14][C:15]=2[C:24]([O:26]C)=O.Cl.[OH-].[NH4+:30]>C1COCC1.C(OCC)(=O)C>[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][N:10]1[C:22]2[CH:21]=[CH:20][CH:19]=[C:18]([OH:23])[C:17]=2[C:16]2[C:11]1=[CH:12][CH:13]=[CH:14][C:15]=2[C:24](=[O:26])[NH2:30]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14923Ammonium HydroxideHCID 22739572HCID 22739572, compound

Product 1

HCID 227396999-[(2,3-Difluorophenyl)methyl]-4-hydroxy-5-carbamoyl carbazoleYield 65%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of the 9-[(2,3-difluorophenyl)methyl]-4-hydroxy-5-carbomethoxy carbazole (514 mg, 1.4 mM) in 5 mL THF and 20 mL concentrated aqueous ammonium hydroxide was stirred at room temperature for 94 hours. The mixture was diluted with ethyl acetate and acidified to pH 1 with 5 N HCl. The aqueous layer was extracted three times with ethyl acetate. The combined organic extracts were washed with H2O and saturated brine, dried over magnesium sulfate, filtered, and concentrated. The residue was purified by column chromatography on silica gel (elution with gradient hexanes/ethyl acetate) to afford 320 mg (65%) of the 9-[(2,3-difluorophenyl)methyl]-4-hydroxy-5-carbamoyl carbazole as a yellow solid. 1H NMR (DMSO-d6) δ 10.45 (s, 1H), 8.8 (br s, 1H), 8.4 (br s, 1H), 7.8 (d, 1H, J=8 Hz), 7.5-7.2 (m, 4H), 7.05 (d, 1H, J=8 Hz), 6.95 (m, 1H), 6.6 (d, 1H, J=8 Hz), 6.35 (t, 1H, J=8 Hz), and 5.9 (s, 2H). IR (KBr, cm−1) 3350, 3125, 1628, 1598, and 1583. MS (ES) m/e 351, 353.

Workup

  1. extractionThe aqueous layer was extracted three times with ethyl acetate
  2. washThe combined organic extracts were washed with H2O and saturated brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography on silica gel (elution with gradient hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-dff02c70e243418689f898874245c2b6
Source dataset
uspto-grants-2001_01
Patent number
US06177440B1

Reaction notes

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