(3S)-3-mercapto-1-(4-nitrobenzyloxycarbonyl)pyrrolidine → (2S,4R)-4-t-butyldimethylsilyloxy-1-(4-nitrobenzyloxycarbonyl)-2-[{(3S)-1-(4-nitrobenzyloxycarbonyl)pyrrolidin-3-ylthio}methyl]pyrrolidine

HRID 346345Notes

Reaction equation

HRID 346345 reaction equation
[SH:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][CH:12]=2)=[O:8])[CH2:3]1.C[O-].[Na+].CO.[Si:25]([O:32][C@H:33]1[CH2:37][N:36]([C:38]([O:40][CH2:41][C:42]2[CH:47]=[CH:46][C:45]([N+:48]([O-:50])=[O:49])=[CH:44][CH:43]=2)=[O:39])[C@H:35]([CH2:51]OS(C)(=O)=O)[CH2:34]1)([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26]>CO.C(OCC)(=O)C>[Si:25]([O:32][C@H:33]1[CH2:37][N:36]([C:38]([O:40][CH2:41][C:42]2[CH:43]=[CH:44][C:45]([N+:48]([O-:50])=[O:49])=[CH:46][CH:47]=2)=[O:39])[C@H:35]([CH2:51][S:1][C@H:2]2[CH2:6][CH2:5][N:4]([C:7]([O:9][CH2:10][C:11]3[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][CH:12]=3)=[O:8])[CH2:3]2)[CH2:34]1)([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26]

Participants

6

Reactant 3

HCID 13219816(3S)-3-mercapto-1-(4-nitrobenzyloxycarbonyl)pyrrolidineHCID 23694274Sodium methanolate methanolHCID 57045968(2S,4R)-4-t-butyldimethylsilyloxy-2-methanesulfonyloxymethyl-1-(4-nitrobenzyloxycarbonyl)pyrrolidine

Product 1

HCID 57062828(2S,4R)-4-t-butyldimethylsilyloxy-1-(4-nitrobenzyloxycarbonyl)-2-[{(3S)-1-(4-nitrobenzyloxycarbonyl)pyrrolidin-3-ylthio}methyl]pyrrolidineYield 70.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (3S)-3-mercapto-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (1.36 g) in methanol (5 ml) was added 28% sodium methoxide-methanol solution (0.97 ml) under ice-cooling and the mixture was stirred at the same temperature for 10 minutes. This solution was added to a solution of (2S,4R)-4-t-butyldimethylsilyloxy-2-methanesulfonyloxymethyl-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (2 g) in methanol (20 ml). The mixture was stirred at ambient temperature for 3 hours and then at 50°-60° C. for 5 hours. The reaction mixture was evaporated in vacuo to give a residue. The residue was dissolved in ethyl acetate (50 ml). The solution was washed with saturated aqueous sodium chloride, dried over magnesium sulfate and evaporated in vacuo. The resulting residue was chromatographed on silica gel (100 g) eluting with a mixture of n-hexane and ethyl acetate (2:1 v/v). The fractions containing the desired compound were collected and evaporated in vacuo to give (2S,4R)-4-t-butyldimethylsilyloxy-1-(4-nitrobenzyloxycarbonyl)-2 -[{(3S)-1-(4-nitrobenzyloxycarbonyl)pyrrolidin-3-ylthio}methyl]pyrrolidine (1.95 g).

Workup

  1. temperaturecooling
  2. stirringThe mixture was stirred at ambient temperature for 3 hours
  3. waitat 50°-60° C. for 5 hours
  4. customThe reaction mixture was evaporated in vacuo
  5. customto give a residue
  6. washThe solution was washed with saturated aqueous sodium chloride
  7. dry with materialdried over magnesium sulfate
  8. customevaporated in vacuo
  9. customThe resulting residue was chromatographed on silica gel (100 g)
  10. washeluting with a mixture of n-hexane and ethyl acetate (2:1 v/v)
  11. additionThe fractions containing the desired compound
  12. customwere collected
  13. customevaporated in vacuo

Sources & evidence

ORD record
ord-394a1628126b4718a7774494f8fae197
Source dataset
uspto-grants-1991_10
Patent number
US05061804

Reaction notes

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