Sodium Azide → (3R,5S)-5-(azidomethyl)-3-(3-chloropropyl)pyrrolidin-2-one

HRID 218437Notes

Reaction equation

HRID 218437 reaction equation
[N+](C1C=CC(S(O[CH2:14][C@@H:15]2[CH2:19][C@@H:18]([CH2:20][CH2:21][CH2:22][Cl:23])[C:17](=[O:24])[NH:16]2)(=O)=O)=CC=1)([O-])=O.[N-:25]=[N+:26]=[N-:27].[Na+].[N-]=[N+]=[N-]>CN(C=O)C>[N:25]([CH2:14][C@H:15]1[NH:16][C:17](=[O:24])[C@H:18]([CH2:20][CH2:21][CH2:22][Cl:23])[CH2:19]1)=[N+:26]=[N-:27]

Participants

5

Reactant 3

HCID 33557Sodium AzideHCID 33558AzideHCID 58011487((2S,4R)-4-(3-chloropropyl)-5-oxopyrrolidin-2-yl)methyl 4-nitrobenzenesulfonate

Product 1

HCID 86637155(3R,5S)-5-(azidomethyl)-3-(3-chloropropyl)pyrrolidin-2-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The ((2S,4R)-4-(3-chloropropyl)-5-oxopyrrolidin-2-yl)methyl 4-nitrobenzenesulfonate (18.05 g, 45.2 mmol) and NaN3 (3.23 g, 49.7 mmol, 1.1 equiv) were stirred in 100 mL of DMF for 19 h. After this time a white solid had formed and LC/MS analysis showed formation of the desired azide. The DMF was removed in vacuo and the residue partitioned between EtOAc/H2O (100+100 mL). The mixture was transferred to a separatory funnel and the layers separated. The aqueous layer was extracted with 100 mL additional EtOAc and the combined organic extracts washed with brine, dried over Na2SO4, filtered and evaporated. The (3R,5S)-5-(azidomethyl)-3-(3-chloropropyl)pyrrolidin-2-one was isolated as a pale yellow syrup (9.08 g, 94% yield).

Workup

  1. customAfter this time a white solid had formed
  2. customThe DMF was removed in vacuo
  3. customthe residue partitioned between EtOAc/H2O (100+100 mL)
  4. customThe mixture was transferred to a separatory funnel
  5. customthe layers separated
  6. extractionThe aqueous layer was extracted with 100 mL additional EtOAc
  7. washthe combined organic extracts washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. customevaporated

Sources & evidence

ORD record
ord-4cf8c6d931fb445c88b74b0b9ee57cf9
Source dataset
uspto-grants-2012_06
Patent number
US08198453B2

Reaction notes

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