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

HRID 567340Notes

Reaction equation

HRID 567340 reaction equation
[F:1][C:2]([F:30])([F:29])[O:3][C:4]1[CH:5]=[C:6]([CH2:10][N:11]2[C:23]3[CH:22]=[CH:21][CH:20]=[C:19]([OH:24])[C:18]=3[C:17]3[C:12]2=[CH:13][CH:14]=[CH:15][C:16]=3[C:25](OC)=[O:26])[CH:7]=[CH:8][CH:9]=1.Cl.[OH-].[NH4+:33]>C1COCC1.C(OCC)(=O)C>[F:1][C:2]([F:30])([F:29])[O:3][C:4]1[CH:5]=[C:6]([CH2:10][N:11]2[C:23]3[CH:22]=[CH:21][CH:20]=[C:19]([OH:24])[C:18]=3[C:17]3[C:12]2=[CH:13][CH:14]=[CH:15][C:16]=3[C:25](=[O:26])[NH2:33])[CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14923Ammonium HydroxideHCID 22738950HCID 22738950, compound

Product 1

HCID 227382239-[(3-Trifluoromethoxyphenyl)methyl]-4-hydroxy-5-carbamoyl carbazoleYield 60%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of the 9-[(3-trifluoromethoxyphenyl)methyl]-4-hydroxy-5-carbomethoxy carbazole (260 mg, 0.62 mM) in 10 mL THF and 30 mL concentrated aqueous ammonium hydroxide was stirred vigorously for 132 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 150 mg (60%) of the 9-[(3-trifluoromethoxyphenyl)methyl]-4-hydroxy-5-carbamoyl carbazole as an off-white solid. 1H NMR (DMSO-d6) δ 10.5 (s, 1H), 8.8 (br s, 1H), 8.4 (br s, 1H), 7.85 (dd, 1H, J=1 and 8 Hz), 7.5-7.15 (m, 5H), 7.1 (d, 1H, J=8 Hz), 7.0 (d, 1H, J=8 Hz), 6.6 (d, 1H, J=8 Hz), 5.95 (d, 1H, J=8 Hz), and 5.65 (s, 2H). IR (KBr, cm−1) 3431, 3203, 1629, 1601, 1580, 1548, 1446, 1330, 1261, 1215, and 777. MS (ES) m/e 399, 401.

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-2c87e86b7ad944e5817610062e104f19
Source dataset
uspto-grants-2001_01
Patent number
US06177440B1

Reaction notes

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