Triethylamine → (S)-1-(2-azido-propyl)-7-methoxy-2,3-dimethyl-1,4-dihydro-indeno[1,2-b]pyrrole

HRID 264471Notes

Reaction equation

HRID 264471 reaction equation
CS(Cl)(=O)=O.[CH3:6][O:7][C:8]1[CH:25]=[C:24]2[C:11]([CH2:12][C:13]3[C:17]([CH3:18])=[C:16]([CH3:19])[N:15]([CH2:20][C@H:21](O)[CH3:22])[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:21]([CH3:22])[CH2:20][N:15]1[C:16]([CH3:19])=[C:17]([CH3:18])[C:13]2[CH2:12][C:11]3[C:24]([C:14]1=2)=[CH:25][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 53908652(R)-1-(7-methoxy-2,3-dimethyl-1,4-dihydro-indeno[1,2-b]pyrrol-1-yl)-propan-2-ol

Product 1

HCID 86751047(S)-1-(2-azido-propyl)-7-methoxy-2,3-dimethyl-1,4-dihydro-indeno[1,2-b]pyrroleYield 48%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

0.7 ml of methanesulfonyl chloride was added dropwise while stirring to a solution, cooled to 0°, of 1.22 g of (R)-1-(7-methoxy-2,3-dimethyl-1,4-dihydro-indeno[1,2-b]pyrrol-1-yl)-propan-2-ol and 2.5 ml of triethylamine in 50 ml of dichloromethane and the mixture was stirred at this temperature for an additional 1.5 hours. The reaction mixture was subsequently diluted with 100 ml of dichloro-methane, washed twice with 60 ml of saturated sodium hydrogen carbonate solution each time and the combined aqueous phases were extracted once with 60 ml of dichloromethane. The combined organic phases were washed with 70 ml of saturated sodium chloride solution, dried over magnesium sulfate and evaporated in a vacuum. The green oil obtained was dissolved in 40 ml of anhydrous dimethylformamide, treated with 0.58 g of sodium azide and the reaction mixture was heated to 80° for 18 hours while stirring. After cooling the solution was poured into 70 ml of water and extracted twice times with 100 ml of ethyl acetate each time. The combined organic phases were washed once with 70 ml of water and once with 70 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). 0.64 g (48%) of (S)-1-(2-azido-propyl)-7-methoxy-2,3-dimethyl-1,4-dihydro-indeno[1,2-b]pyrrole were obtained as a light yellow oil.

Workup

  1. stirringthe mixture was stirred at this temperature for an additional 1.5 hours
  2. washwashed twice with 60 ml of saturated sodium hydrogen carbonate solution each time
  3. extractionthe combined aqueous phases were extracted once with 60 ml of dichloromethane
  4. washThe combined organic phases were washed with 70 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 80° for 18 hours
  9. stirringwhile stirring
  10. temperatureAfter cooling the solution
  11. extractionextracted twice times with 100 ml of ethyl acetate each time
  12. washThe combined organic phases were washed once with 70 ml of water and once with 70 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-7f27dafa93b04a9fb821e58641f1512f
Source dataset
uspto-grants-1997_07
Patent number
US05646173

Reaction notes

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