Pyridiniumtribromide → Methyl-2-bromo-7-chloro-3-cyclohexyl-1H-indole-6-carboxylate

HRID 1672144Notes

Reaction equation

HRID 1672144 reaction equation
[Cl:1][C:2]1[C:3]([C:17]([O:19][CH3:20])=[O:18])=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][CH:8]=[C:7]2[CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1.[Br-:21].[Br-].[Br-].[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1>C1COCC1.C(Cl)Cl.C(Cl)Cl>[Br:21][C:8]1[NH:9][C:10]2[C:6]([C:7]=1[CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)=[CH:5][CH:4]=[C:3]([C:17]([O:19][CH3:20])=[O:18])[C:2]=2[Cl:1]

Participants

5

Reactant 2

HCID 21124087PyridiniumtribromideHCID 59802485methyl 7-chloro-3-cyclohexyl-1H-indole-6-carboxylate

Product 1

HCID 59802493Methyl-2-bromo-7-chloro-3-cyclohexyl-1H-indole-6-carboxylateYield 66.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21919333Tetrahydrofurane dichloromethaneSolvent

Procedure

To a mixture of the methyl 7-chloro-3-cyclohexyl-1H-indole-6-carboxylate (1 g, 3.43 mmol) in a mixture of THF/CH2Cl2 (9 ml/9 ml) at r.t. under N2 was added pyridinium tribromide (1.33 g, 4.16 mmol, recrystallized from AcOH), and the reaction mixture stirred at r.t. for 2 hr. The mixture was then diluted with CH2Cl2 (40 ml), and the organics washed with NaHCO3 (30 ml, sat. aq.), followed by hydrochloric acid (30 ml, 1N) and brine (30 ml). After concentration of the organic layer, the residue was purified by Biotage flash chromatography (gradient elution, 0 to 20% EtOAc/Hexane) to gave methyl 2-bromo-7-chloro-3-cyclohexyl-1H-indole-6-carboxylate (841.8 mg, 66%) and to recover the starting material (201 mg). 1H NMR (500 MHz): (CD3OD) δ 7.67 (b d, J=8.5, 1H), 7.59 (d, J=8.5, 1H), 3.93 (s, 3H), 2.89 (m, 1H), 2.00-1.90 (overlapping m, 4H), 1.83-1.78 (overlapping m, 3H), 1.50-1.40 (m, 3H); Analytical HPLC method: Solvent A=10% MeOH-90% H2O-0.1% TFA, Solvent B=90% MeOH-10% H2O-0.1% TFA, Start % B=0, Final % B=100, Gradient time=2 min, Flow Rate=5 ml/min, Column: Xterra MS C18 S7 3.0×50 mm; LC/MS: (ES+) m/z (M+H)+=370.02, 372.03, 374.02, HPLC Rt=2.002 min.

Workup

  1. washthe organics washed with NaHCO3 (30 ml, sat. aq.)
  2. customAfter concentration of the organic layer, the residue was purified by Biotage flash chromatography (gradient elution, 0 to 20% EtOAc/Hexane)

Sources & evidence

ORD record
ord-03916f5b5b4847a7a514be3293363161
Source dataset
uspto-grants-2011_08
Patent number
US07998951B2

Reaction notes

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