Triethylamine → (S)-1-(2-azido-propyl)-7-methoxy-4,4-dimethyl-1,4-dihydro-indeno[1,2-b]pyrrole

HRID 264368Notes

Reaction equation

HRID 264368 reaction equation
CS(Cl)(=O)=O.[CH3:6][O:7][C:8]1[CH:23]=[C:22]2[C:11]([C:12]([CH3:25])([CH3:24])[C:13]3[CH:17]=[CH:16][N:15]([CH2:18][C@H:19](O)[CH3:20])[C:14]=32)=[CH:10][CH:9]=1.C(N(CC)CC)C.[N-:33]=[N+:34]=[N-:35].[Na+]>ClCCl.CN(C)C=O.O>[N:33]([C@@H:19]([CH3:20])[CH2:18][N:15]1[CH:16]=[CH:17][C:13]2[C:12]([CH3:25])([CH3:24])[C:11]3[C:22]([C:14]1=2)=[CH:23][C:8]([O:7][CH3:6])=[CH:9][CH:10]=3)=[N+:34]=[N-:35]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 33557Sodium AzideHCID 54520992(R)-1-(7-methoxy-4,4-dimethyl-1,4-dihydro-indeno[1,2-b]pyrrol-1-yl)-propan-2-ol

Product 1

HCID 10709056(S)-1-(2-azido-propyl)-7-methoxy-4,4-dimethyl-1,4-dihydro-indeno[1,2-b]pyrroleYield 50.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

2.0 ml of methanesulfonyl chloride were added dropwise while stirring to a solution, cooled to 0°, of 3.42 g of (R)-1-(7-methoxy-4,4-dimethyl-1,4-dihydro-indeno[1,2-b]pyrrol-1-yl)-propan-2-ol and 7.3 ml of triethylamine in 70 ml of dichloromethane, and the mixture was stirred at this temperature for an additional 1.5 hours. The reaction mixture was subsequently diluted with 170 ml of dichloromethane, washed twice with 90 ml of saturated sodium hydrogen carbonate solution each time and the combined aqueous phases were extracted once with 70 ml of dichloromethane. The combined organic phases were washed with 90 ml of saturated sodium chloride solution, dried over magnesium sulfate and evaporated in a vacuum. The green oil obtained was dissolved in 70 ml of anhydrous dimethylformamide, treated with 1.35 g of sodium azide and the reaction mixture was heated to 60° for 20 hours while stirring. After cooling, the solution was poured into 100 ml of water and extracted three times with 100 ml of ethyl acetate 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 (hexane/ethyl acetate 4:1). 1.89 g (50%) of (S)-1-(2-azido-propyl)-7-methoxy-4,4-dimethyl-1,4-dihydro-indeno[1,2-b]pyrrole were obtained as a yellow oil.

Workup

  1. stirringthe mixture was stirred at this temperature for an additional 1.5 hours
  2. washwashed twice with 90 ml of saturated sodium hydrogen carbonate solution each time
  3. extractionthe combined aqueous phases were extracted once with 70 ml of dichloromethane
  4. washThe combined organic phases were washed with 90 ml of saturated sodium chloride solution
  5. dry with materialdried over magnesium sulfate
  6. customevaporated in a vacuum
  7. customThe green oil obtained
  8. temperaturethe reaction mixture was heated to 60° for 20 hours
  9. stirringwhile stirring
  10. temperatureAfter cooling
  11. extractionextracted three times with 100 ml of ethyl acetate 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 (hexane/ethyl acetate 4:1)

Sources & evidence

ORD record
ord-27b1fcb42ee44b7c9271affa87ad4f8c
Source dataset
uspto-grants-1997_07
Patent number
US05646173

Reaction notes

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