Ethyl Acetate → 1-[7-(6-Chloro-indole-1-sulfonyl)-4,4-dimethyl-3,4-dihydro-1H-isoquinolin-2-yl]-ethanone

HRID 22819

Reaction equation

HRID 22819 reaction equation
CC(C)([O-])C.[K+].[Cl:7][C:8]1[CH:16]=[C:15]2[C:11]([CH:12]=[CH:13][NH:14]2)=[CH:10][CH:9]=1.[C:17]([N:20]1[CH2:29][C:28]([CH3:31])([CH3:30])[C:27]2[C:22](=[CH:23][C:24]([S:32](Cl)(=[O:34])=[O:33])=[CH:25][CH:26]=2)[CH2:21]1)(=[O:19])[CH3:18].C(OCC)(=O)C>O1CCCC1.O>[Cl:7][C:8]1[CH:16]=[C:15]2[C:11]([CH:12]=[CH:13][N:14]2[S:32]([C:24]2[CH:23]=[C:22]3[C:27]([C:28]([CH3:31])([CH3:30])[CH2:29][N:20]([C:17](=[O:19])[CH3:18])[CH2:21]3)=[CH:26][CH:25]=2)(=[O:33])=[O:34])=[CH:10][CH:9]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 871116-ChloroindoleHCID 225920232-Acetyl-4,4-dimethyl-1,2,3,4-tetrahydro-isoquinoline-7-sulfonyl ChlorideHCID 23665647Potassium tert-butoxide

Product 1

HCID 225920261-[7-(6-Chloro-indole-1-sulfonyl)-4,4-dimethyl-3,4-dihydro-1H-isoquinolin-2-yl]-ethanoneYield 51%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Potassium tert-butoxide (37 mg, 0.33 mmol) was added to a stirred solution of 6-chloroindole (50 mg, 0.33 mmol) in dry tetrahydrofuran (1 ml) under argon at room temperature. After stirring for 5 minutes, a solution of 2-acetyl-4,4-dimethyl-1,2,3,4-tetrahydro-isoquinoline-7-sulfonyl chloride (D3) (100 mg, 0.33 mmol) in dry tetrahydrofuran (1 ml) was added and the solution was stirred for a further 3 h. Ethyl acetate (5 ml) and water (5 ml) were added to the reaction mixture, which was then shaken. The layers were separated and the organic phase was washed with brine (5 ml), dried (MgSO4) and concentrated in vacuo to an oil. The oil was purified by column chromatography over silica gel eluting with a gradient of acetone/toluene to afford the title compound (D4) (70 mg, 51%), MS: m/z (MH+) 417/419.

Workup

  1. stirringthe solution was stirred for a further 3 h
  2. stirringwas then shaken
  3. customThe layers were separated
  4. washthe organic phase was washed with brine (5 ml)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo to an oil
  7. customThe oil was purified by column chromatography over silica gel eluting with a gradient of acetone/toluene

Sources & evidence

ORD record
ord-a915c780e31247d2aa26832773c9cdd8
Source dataset
uspto-grants-2005_02
Patent number
US06849644B2

Linked notes

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