Sodium hydride → (2S,4R)-4-t-butyldimethylsilyloxy-2-(1-methyl-1H-tetrazol-5-yl)thiomethyl-1-(4-nitrobenzyloxycarbonyl)pyrrolidine

HRID 1088968Notes

Reaction equation

HRID 1088968 reaction equation
[H-].[Na+].[SH:3][C:4]1[N:8]([CH3:9])[N:7]=[N:6][N:5]=1.[Si:10]([O:17][C@H:18]1[CH2:22][N:21]([C:23]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][C:30]([N+:33]([O-:35])=[O:34])=[CH:29][CH:28]=2)=[O:24])[C@H:20]([CH2:36]OS(C)(=O)=O)[CH2:19]1)([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11]>CN(C)C=O>[Si:10]([O:17][C@H:18]1[CH2:22][N:21]([C:23]([O:25][CH2:26][C:27]2[CH:28]=[CH:29][C:30]([N+:33]([O-:35])=[O:34])=[CH:31][CH:32]=2)=[O:24])[C@H:20]([CH2:36][S:3][C:4]2[N:8]([CH3:9])[N:7]=[N:6][N:5]=2)[CH2:19]1)([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 57045968(2S,4R)-4-t-butyldimethylsilyloxy-2-methanesulfonyloxymethyl-1-(4-nitrobenzyloxycarbonyl)pyrrolidineHCID 178482017HCID 178482017, compound

Product 1

HCID 18641558(2S,4R)-4-t-butyldimethylsilyloxy-2-(1-methyl-1H-tetrazol-5-yl)thiomethyl-1-(4-nitrobenzyloxycarbonyl)pyrrolidineYield 53.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of sodium hydride (62.8% suspension in oil) (0.38 g) in N,N-dimethylformamide (12 ml) was added 5-mercapto-1-methyl-1H-tetrazole (1.14 g) under ice-cooling. The mixture was stirred at the same temperature for 30 minutes. This solution was added dropwise to a solution of (2S,4R)-4-t-butyldimethylsilyloxy-2-methanesulfonyloxymethyl-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (3.0 g) in N,N-dimethylformamide (60 ml) under ice-cooling. The mixture was stirred at 60°-70° C. for 2 hours. The reaction mixture was poured into ice-water (200 ml) and extracted 3 times with ethyl acetate (100 ml). The extracts were combined, washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and evaporated in vacuo. The resulting residue was chromatographed on silica gel (100 g) eluting with a mixture of dichloromethane and acetone (40:1, V/V). The fractions containing the desired compound were collected and concentrated under reduced pressure to give (2S,4R)-4-t-butyldimethylsilyloxy-2-(1-methyl-1H-tetrazol- 5-yl)thiomethyl-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (1.68 g).

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. stirringThe mixture was stirred at 60°-70° C. for 2 hours
  4. extractionextracted 3 times with ethyl acetate (100 ml)
  5. washwashed with saturated aqueous sodium chloride
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customevaporated in vacuo
  8. customThe resulting residue was chromatographed on silica gel (100 g)
  9. washeluting with a mixture of dichloromethane and acetone (40:1, V/V)
  10. additionThe fractions containing the desired compound
  11. customwere collected
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-640bb00605c44bd1828949ac2dfb8460
Source dataset
uspto-grants-1990_10
Patent number
US04963543

Reaction notes

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