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

HRID 523240Notes

Reaction equation

HRID 523240 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[F: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]([F: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 1177608524-bromo-7-(ethoxycarbonyl)-3-fluoro-9H-carbazole-1-carboxylic acid

Product 1

HCID 117761209ethyl 5-bromo-8-carbamoyl-6-fluoro-9H-carbazole-2-carboxylateYield 95%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 4-bromo-7-(ethoxycarbonyl)-3-fluoro-9H-carbazole-1-carboxylic acid (2.39 g, 6.29 mmol), EDC (1.81 g, 9.43 mmol) and HOBT (1.44 g, 9.43 mmol) in THF (30 mL) and DCM (5 mL) was stirred at room temperature for 20 min Ammonium hydroxide (0.367 mL, 9.43 mmol) was added, and the mixture was stirred at room temperature for 4 h. The mixture was diluted with EtOAc, washed twice with saturated aqueous NaHCO3, then with brine. The aqueous layers were extracted with EtOAc, and the combined organic layers were dried and concentrated. The residue was triturated with MeOH with sonication to provide ethyl 5-bromo-8-carbamoyl-6-fluoro-9H-carbazole-2-carboxylate as a pale yellow solid (2.26 g, 95% yield). Mass spectrum m/z 379, 381 (M+H)+. 1H NMR (500 MHz, DMSO-d6) δ 12.02 (s, 1H), 8.70 (d, J=8.3 Hz, 1H), 8.51 (d, J=1.1 Hz, 1H), 8.29 (br. s., 1H), 8.10 (d, J=10.3 Hz, 1H), 7.87 (dd, J=8.5, 1.5 Hz, 1H), 7.74 (br. s., 1H), 4.37 (q, J=6.9 Hz, 2H), and 1.37 (t, J=7.1 Hz, 3H). 1H NMR (500 MHz, MeOH-d4) δ 8.77 (d, J=8.2 Hz, 1H), 8.36 (d, J=0.9 Hz, 1H), 7.83 (d, J=8.2 Hz, 1H), 7.46 (d, J=8.2 Hz, 1H), 4.12 (q, J=7.0 Hz, 2H), 1.58-1.36 (m, 4H), and 1.26 (t, J=7.2 Hz, 3H).

Workup

  1. additionwas added
  2. washwashed twice with saturated aqueous NaHCO3
  3. extractionThe aqueous layers were extracted with EtOAc
  4. customthe combined organic layers were dried
  5. concentrationconcentrated
  6. customThe residue was triturated with MeOH with sonication

Sources & evidence

ORD record
ord-0c8068a6cee946a288636017d9a070c1
Source dataset
uspto-grants-2016_05
Patent number
US09334290B2

Reaction notes

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