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

HRID 1672144ノート

反応式

HRID 1672144 の反応式
[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]

参加物

5

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 21919333Tetrahydrofurane dichloromethane溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-03916f5b5b4847a7a514be3293363161
出典データセット
uspto-grants-2011_08
特許番号
US07998951B2

反応ノート

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