((2-Chloroethyl)sulphonyl)benzene → tert-Butyl 6-[2-(phenylsulfonyl)ethyl]-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate

HRID 1071058Notes

Reaction equation

HRID 1071058 reaction equation
[CH2:1]1[C:14]2[C:13]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[NH:7][C:6]=2[CH2:5][CH2:4][N:3]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:2]1.[OH-].[K+].[C:24]1([S:30]([CH2:33][CH2:34]Cl)(=[O:32])=[O:31])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>C(Cl)Cl.S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC>[C:24]1([S:30]([CH2:33][CH2:34][N:7]2[C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:13]=3[C:14]3[CH2:1][CH2:2][N:3]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:4][CH2:5][C:6]2=3)(=[O:32])=[O:31])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

6

Reactant 3

HCID 13646((2-Chloroethyl)sulphonyl)benzeneHCID 14797Potassium HydroxideHCID 22396759tert-butyl 1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate

Product 1

HCID 22396854tert-Butyl 6-[2-(phenylsulfonyl)ethyl]-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylateYield 87.3%

Reagents, catalysts & solvents 2

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 6344DichloromethaneSolvent

Procedure

tert-Butyl 1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (0.111 g, 0.388 mmol) was dissolved in CH2Cl2 (10 mL) and this solution was added to a mixture of 50% aqueous KOH (5 mL) and tetrabutylammonium hydrogen sulfate (0.100 g). The biphasic mixture was stirred vigorously at rt. 2-Chloroethyl phenyl sulfone (0.318 g, 1.55 mmol) was added, then the reaction mixture was stirred for 4 h. The organic phase was separated and the aqueous phase was extracted with CH2Cl2. The combined organic layers was concentrated. The crude product was chromatographed (Biotage 40s SiO2 column, eluted with a 10% to 40% EtOAc in hexane gradient) to give tert-butyl 6-[2-(phenylsulfonyl)ethyl]-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (0.154 g) in 87% as a clear solid. 1H NMR (300 MHz, CDCl3) δ 1.48, 2.87-2.93, 3.38-3.42, 3.63, 3.69, 4.52, 7.04-7.17, 7.42, 7.53-7.59, 7.63-7.70, 7.88.

Workup

  1. stirringthe reaction mixture was stirred for 4 h
  2. customThe organic phase was separated
  3. extractionthe aqueous phase was extracted with CH2Cl2
  4. concentrationThe combined organic layers was concentrated
  5. customThe crude product was chromatographed (Biotage 40s SiO2 column
  6. washeluted with a 10% to 40% EtOAc in hexane gradient)

Sources & evidence

ORD record
ord-bba4173e3d304205945abfe7bc0669ae
Source dataset
uspto-grants-2005_06
Patent number
US06903090B2

Reaction notes

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