1,2-Dichloroethane → ethyl 5-bromo-8-carbamoyl-2,3,4,9-tetrahydro-1H-carbazole-2-carboxylate

HRID 661892Notes

Reaction equation

HRID 661892 reaction equation
[Br:1][C:2]1[CH:14]=[CH:13][C:12]([C:15](O)=[O:16])=[C:11]2[C:3]=1[C:4]1[CH2:5][CH2:6][CH:7]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:8][C:9]=1[NH:10]2.C(Cl)CCl.C1C=CC2N(O)N=[N:33]C=2C=1.[OH-].[NH4+]>C1COCC1.C(Cl)Cl>[Br:1][C:2]1[CH:14]=[CH:13][C:12]([C:15](=[O:16])[NH2:33])=[C:11]2[C:3]=1[C:4]1[CH2:5][CH2:6][CH:7]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:8][C:9]=1[NH:10]2

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 14923Ammonium HydroxideHCID 757711-HydroxybenzotriazoleHCID 593750655-bromo-2-(ethoxycarbonyl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxylic acid2×

Product 1

HCID 59375013ethyl 5-bromo-8-carbamoyl-2,3,4,9-tetrahydro-1H-carbazole-2-carboxylateYield 72.9%

Reagents, catalysts & solvents 1

HCID 21919333Tetrahydrofurane dichloromethaneSolvent

Procedure

A suspension of 5-bromo-2-(ethoxycarbonyl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxylic acid (Intermediate 46-1, 12.28 g, 33.5 mmol), EDC (7.71 g, 40.2 mmol), and HOBT (6.16 g, 40.2 mmol) in THF-DCM (4:1, 335 mL) was treated with 28% aqueous ammonium hydroxide (7.83 mL, 201 mmol), and the resulting suspension was stirred at rt overnight. The mixture was concentrated and the residue was suspended in water. The precipitate was collected by filtration, washed with water and EtOAc and dried to give ethyl 5-bromo-8-carbamoyl-2,3,4,9-tetrahydro-1H-carbazole-2-carboxylate (8.92 g). The filtrate was concentrated and the residue was suspended in methanol. A solid was collected by filtration, washed with methanol and air dried to afford additional product (0.39 g) for a total of 9.31 g (76%). 1H NMR (400 MHz, DMSO-d6) δ 11.08 (s, 1H) 8.02 (br. s., 1H) 7.43 (d, J=8.13 Hz, 1H) 7.39 (br. s., 1H) 7.14 (d, J=8.13 Hz, 1H) 4.02-4.17 (m, 2H) 3.07-3.18 (m, 1H) 2.97-3.06 (m, 1H) 2.86-2.98 (m, 2H) 2.77-2.86 (m, 1H) 2.09-2.19 (m, 1H) 1.72-1.86 (m, 1H) 1.20 (t, J=7.14 Hz, 3H). Mass spectrum m/z 365, 367 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated
  2. filtrationThe precipitate was collected by filtration
  3. washwashed with water and EtOAc
  4. customdried

Sources & evidence

ORD record
ord-50ec2a011b424902a80582a9127d3bf5
Source dataset
uspto-grants-2011_12
Patent number
US08084620B2

Reaction notes

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