1,2-Dichloroethane → HCID 59375131, compound

HRID 1811073Notes

Reaction equation

HRID 1811073 reaction equation
[Br:1][C:2]1[CH:14]=[CH:13][C:12]([C:15]([OH:17])=O)=[C:11]2[C:3]=1[C:4]1[CH2:5][CH2:6][CH2:7][CH2:8][C:9]=1[NH:10]2.C1C=[N:22]C2N(O)N=NC=2C=1.C(Cl)CCl.N>C1COCC1.O.CCOC(C)=O.C(Cl)Cl>[Br:1][C:2]1[CH:14]=[CH:13][C:12]([C:15]([NH2:22])=[O:17])=[C:11]2[C:3]=1[C:4]1[CH2:5][CH2:6][CH2:7][CH2:8][C:9]=1[NH:10]2

Participants

9

Reactant 4

HCID 111,2-DichloroethaneHCID 222Ammonia2×HCID 181649HOAtHCID 66606262HCID 66606262, compound

Product 1

HCID 59375131HCID 59375131, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 5-bromo-2,3,4,9-tetrahydro-1H-carbazole-8-carboxylic acid (Intermediate 46-3, 70% purity, mixed with Intermediate 47-3 from an incomplete reaction done according to the procedure used to prepare Intermediate 47-1; 3 g, 7.14 mmol) in THF (80 mL) and DCM (20 mL) was treated with HOAT (1.166 g, 8.57 mmol) and EDC (1.642 g, 8.57 mmol). The mixture was stirred at rt for 2.5 h, then was treated with anhydrous ammonia gas for ca. 2 min, forming a very thick slurry. The mixture was stirred for 30 min, then was treated again with ammonia gas for ca. 1 min. After stirring for another hour, the mixture was diluted with water and EtOAc (dissolving the solid). The layers were separated and the aqueous phase was extracted again with EtOAc. The combined organic layers were washed twice with 0.1 M aqueous sodium hydroxide, then with 1 M hydrochloric acid and brine, dried and concentrated to provide 5-bromo-2,3,4,9-tetrahydro-1H-carbazole-8-carboxamide as a pale orange-tan solid (2.47 g, 84%, including the product from the incomplete reaction yielding the starting material). 1H NMR (400 MHz, DMSO-d6) δ 10.95 (1H, s), 8.02 (1H, br. s.), 7.44 (1H, d, J=7.9 Hz), 7.38 (1H, br. s.), 7.14 (1H, d, J=8.1 Hz), 2.99 (2H, br. s.), 2.75 (2H, br. s.), 1.78 (4H, br. s.). Mass spectrum m/z 293, 295 (M+H)+.

Workup

  1. customforming a very thick slurry
  2. stirringThe mixture was stirred for 30 min
  3. stirringAfter stirring for another hour
  4. dissolutiondissolving the solid)
  5. customThe layers were separated
  6. extractionthe aqueous phase was extracted again with EtOAc
  7. washThe combined organic layers were washed twice with 0.1 M aqueous sodium hydroxide
  8. dry with materialwith 1 M hydrochloric acid and brine, dried
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-4a7cd462f4e44783ad5fa16864a172bd
Source dataset
uspto-grants-2013_01
Patent number
US08362065B2

Reaction notes

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