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

HRID 1672144노트

반응식

HRID 1672144 반응식
[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]

참가 물질

5

반응물 2

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

생성물 1

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

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 21919333Tetrahydrofurane dichloromethane용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-03916f5b5b4847a7a514be3293363161
출처 데이터셋
uspto-grants-2011_08
특허 번호
US07998951B2

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