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

HRID 1811072Notes

Reaction equation

HRID 1811072 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-cfbe0c1a2f35430d8c7671ea81f9be1a
Source dataset
uspto-grants-2013_01
Patent number
US08362065B2

Reaction notes

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