Lithium Hydroxide → 6-bromo-8-carbamoyl-9H-carbazole-2-carboxylic acid

HRID 2410669Notes

Reaction equation

HRID 2410669 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:12](=[C:13]([C:15](=[O:17])[NH2:16])[CH:14]=1)[NH:11][C:10]1[CH:9]=[C:8]([C:18]([O:20]CC)=[O:19])[CH:7]=[CH:6][C:5]2=1.[OH-].[Li+]>C1COCC1.CCO.O>[Br:1][C:2]1[CH:3]=[C:4]2[C:12](=[C:13]([C:15](=[O:17])[NH2:16])[CH:14]=1)[NH:11][C:10]1[CH:9]=[C:8]([C:18]([OH:20])=[O:19])[CH:7]=[CH:6][C:5]2=1

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 66604694ethyl 6-bromo-8-carbamoyl-9H-carbazole-2-carboxylate

Product 1

HCID 666048126-bromo-8-carbamoyl-9H-carbazole-2-carboxylic acidYield 284.9%

Reagents, catalysts & solvents 1

HCID 18504229Ethanol tetrahydrofuran waterSolvent

Procedure

A solution of ethyl 6-bromo-8-carbamoyl-9H-carbazole-2-carboxylate (4.7 g, 8.85 mmol) and lithium hydroxide (0.848 g, 35 4 mmol) in THF/EtOH/H2O (3/1/1) (70 mL) was heated at 75° C. overnight. The reaction was concentrated and the resulting yellow solid was suspended in water. To above suspension, was added 1M HCl/conc. HCl until pH=2-3. The light yellow solid was collected by filtration and air-dried to furnish 8.4 g of 6-bromo-8-carbamoyl-9H-carbazole-2-carboxylic acid with ˜80% purity. This material was carried forward to the next step. MS (ESI) m/z−=331/363 [M−H]−, 1 Br isotope pattern. HPLC retention time 9.79 min. (Sunfire C18 3.5 μm, 4.6×150 mm column, 15 min gradient, 10-100% B, 1 mL/min. Solvent A: 5% CH3CN-95% H2O-0.1% TFA; Solvent B: 95% CH3CN-5% H2O-0.1% TFA). 1H NMR (DMSO-d6) δ ppm 13.0-12.65 (b, 1H), 11.80 (s, 1H), 8.65 (d, 1H, J=1.8), 8.39 (d, 1H, J=0.6), 8.30 (s, 1H), 8.29 (d, 1H, J=8.2), 8.20 (d, 1H, J=1.8), 7.79 (dd, 1H, J=1.5, 8.3), 7.66 (br. s., 1H).

Workup

  1. concentrationThe reaction was concentrated
  2. additionTo above suspension, was added 1M HCl/conc
  3. filtrationThe light yellow solid was collected by filtration
  4. customair-dried

Sources & evidence

ORD record
ord-2f48d43c555c4c46a28c78c0c9c9a942
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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