Triethylamine → (S)-1-(2-azido-propyl)-4,5-dihydro-8-methoxy-1H-benz[g]indole

HRID 264377Notes

Reaction equation

HRID 264377 reaction equation
CS(Cl)(=O)=O.[CH3:6][O:7][C:8]1[CH:24]=[CH:23][C:11]2[CH2:12][CH2:13][C:14]3[CH:15]=[CH:16][N:17]([CH2:19][C@H:20](O)[CH3:21])[C:18]=3[C:10]=2[CH:9]=1.C(N(CC)CC)C.[N-:32]=[N+:33]=[N-:34].[Na+]>ClCCl.C(OCC)C.CN(C)C=O.O>[N:32]([C@@H:20]([CH3:21])[CH2:19][N:17]1[C:18]2[C:10]3[CH:9]=[C:8]([O:7][CH3:6])[CH:24]=[CH:23][C:11]=3[CH2:12][CH2:13][C:14]=2[CH:15]=[CH:16]1)=[N+:33]=[N-:34]

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 33557Sodium AzideHCID 54152718(R)-1-(4,5-dihydro-8-methoxy-1H-benz[g]indol-1-yl)-propan-2-ol

Product 1

HCID 54279252(S)-1-(2-azido-propyl)-4,5-dihydro-8-methoxy-1H-benz[g]indoleYield 72.1%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

1.4 ml of methanesulfonyl chloride were added dropwise while stirring to a solution, cooled to 0° C., of 2.25 g of (R)-1-(4,5-dihydro-8-methoxy-1H-benz[g]indol-1-yl)-propan-2-ol and 5 ml of triethyl-amine in 60 ml of dichloromethane and the mixture was stirred at this temperature for an additional 1.5 hours. The reaction mixture was subsequently diluted with 300 ml of diethyl ether, washed twice with 100 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases were extracted once with 100 ml of diethyl ether. The combined organic phases were washed with 100 ml of saturated sodium chloride solution, dried over magnesium sulfate and evaporated in a vacuum. The brown oil obtained was dissolved in 50 ml of anhydrous dimethyl formamide, treated with 1.17 g of sodium azide and the reaction mixture was heated to 60° for 15 hours while stirring. After cooling, the solution was poured into 140 ml of water and extracted twice with 140 ml of diethyl ether each time. The combined organic phases were washed once with 100 ml of water and once with 100 ml of saturated sodium chloride solution, dried over magnesium sulfate and the solution was concentrated in a vacuum. The brown oil obtained was purified by column chromatography on silica gel (toluene). 1.78 g (71%) of (S)-1-(2-azido-propyl)-4,5-dihydro-8-methoxy-1H-benz[g]indole were obtained as a colorless oil.

Workup

  1. stirringthe mixture was stirred at this temperature for an additional 1.5 hours
  2. washwashed twice with 100 ml of saturated sodium hydrogen carbonate solution
  3. extractionthe combined aqueous phases were extracted once with 100 ml of diethyl ether
  4. washThe combined organic phases were washed with 100 ml of saturated sodium chloride solution
  5. dry with materialdried over magnesium sulfate
  6. customevaporated in a vacuum
  7. customThe brown oil obtained
  8. temperaturethe reaction mixture was heated to 60° for 15 hours
  9. stirringwhile stirring
  10. temperatureAfter cooling
  11. extractionextracted twice with 140 ml of diethyl ether each time
  12. washThe combined organic phases were washed once with 100 ml of water and once with 100 ml of saturated sodium chloride solution
  13. dry with materialdried over magnesium sulfate
  14. concentrationthe solution was concentrated in a vacuum
  15. customThe brown oil obtained
  16. customwas purified by column chromatography on silica gel (toluene)

Sources & evidence

ORD record
ord-2612dac2b15a4b6bb969894df5f8e449
Source dataset
uspto-grants-1997_07
Patent number
US05646173

Reaction notes

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