1,2-Dichloroethane → ethyl 5-bromo-8-carbamoyl-6-methyl-9H-carbazole-2-carboxylate

HRID 523250Notes

Reaction equation

HRID 523250 reaction equation
[Br:1][C:2]1[C:14]2[C:13]3[C:8](=[CH:9][C:10]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:11][CH:12]=3)[NH:7][C:6]=2[C:5]([C:20](O)=[O:21])=[CH:4][C:3]=1[CH3:23].C(Cl)CCl.C1C=CC2N(O)N=[N:34]C=2C=1.[OH-].[NH4+]>C1COCC1.C(Cl)Cl.CCOC(C)=O>[Br:1][C:2]1[C:3]([CH3:23])=[CH:4][C:5]([C:20](=[O:21])[NH2:34])=[C:6]2[C:14]=1[C:13]1[CH:12]=[CH:11][C:10]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:9][C:8]=1[NH:7]2

Participants

8

Reactant 4

HCID 111,2-DichloroethaneHCID 14923Ammonium HydroxideHCID 757711-HydroxybenzotriazoleHCID 1177712304-bromo-7-(ethoxycarbonyl)-3-methyl-9H-carbazole-1-carboxylic acid

Product 1

HCID 117761166ethyl 5-bromo-8-carbamoyl-6-methyl-9H-carbazole-2-carboxylateYield 91%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 4-bromo-7-(ethoxycarbonyl)-3-methyl-9H-carbazole-1-carboxylic acid (1.40 g, 3.72 mmol), EDC (1.070 g, 5.58 mmol), and HOBT (0.855 g, 5.58 mmol) in a mixture of THF (30 mL) and DCM (5 mL) was stirred at room temperature for 60 min. Ammonium hydroxide (0.217 mL, 5.58 mmol) was added, and the mixture was stirred at room temperature overnight. The mixture was diluted with EtOAc and washed with saturated aqueous NaHCO3. Phase separation could not be achieved, so the mixture was filtered, and the collected solid was washed sequentially with water and EtOAc, triturated with MeOH and dried. The EtOAc-water filtrate was separated and the organic phase was washed with brine, dried and concentrated. The residue was triturated with MeOH, and the resulting solid was combined with the first solid to give ethyl 5-bromo-8-carbamoyl-6-methyl-9H-carbazole-2-carboxylate as an off-white solid (1.27 g, 91% yield). Mass spectrum m/z 375, 377 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ 11.88 (s, 1H), 8.77 (d, J=8.6 Hz, 1H), 8.48 (d, J=0.9 Hz, 1H), 8.20 (br. s., 1H), 7.84 (dd, J=8.5, 1.4 Hz, 1H), 7.59 (br. s., 1H), 4.37 (q, J=7.0 Hz, 2H), 2.55 (s, 3H), and 1.37 (t, J=7.0 Hz, 3H).

Workup

  1. stirringthe mixture was stirred at room temperature overnight
  2. washwashed with saturated aqueous NaHCO3
  3. customPhase separation could not
  4. filtrationwas filtered
  5. washthe collected solid was washed sequentially with water and EtOAc
  6. customtriturated with MeOH
  7. customdried
  8. customThe EtOAc-water filtrate was separated
  9. washthe organic phase was washed with brine
  10. customdried
  11. concentrationconcentrated
  12. customThe residue was triturated with MeOH

Sources & evidence

ORD record
ord-78f93df8770449efa03d35564c268535
Source dataset
uspto-grants-2016_05
Patent number
US09334290B2

Reaction notes

Loading…