(2S,4S)-4-(4-methoxybenzyl)thio-1-(4-nitrobenzyloxycarbonyl)-L-proline → HCID 10771163, compound

HRID 362060Notes

Reaction equation

HRID 362060 reaction equation
[CH3:1][O:2][C:3]1[CH:31]=[CH:30][C:6]([CH2:7][S:8][C@@H:9]2[CH2:13][N:12]([C:14]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][CH:19]=3)=[O:15])[C@H:11]([C:27]([OH:29])=O)[CH2:10]2)=[CH:5][CH:4]=1.FC(F)(F)C(O)=O.FC(F)(F)C(O)=O.[N+:46]([C:49]1[CH:66]=[CH:65][C:52]([CH2:53][O:54][C:55]([CH2:57][N:58]2[CH2:64][CH2:63][CH2:62][NH:61][CH2:60][CH2:59]2)=[O:56])=[CH:51][CH:50]=1)([O-:48])=[O:47]>C(#N)C.C(N(C(C)C)CC)(C)C>[CH3:1][O:2][C:3]1[CH:31]=[CH:30][C:6]([CH2:7][S:8][C@@H:9]2[CH2:13][N:12]([C:14]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][CH:19]=3)=[O:15])[C@H:11]([C:27]([N:61]3[CH2:62][CH2:63][CH2:64][N:58]([CH2:57][C:55]([O:54][CH2:53][C:52]4[CH:65]=[CH:66][C:49]([N+:46]([O-:48])=[O:47])=[CH:50][CH:51]=4)=[O:56])[CH2:59][CH2:60]3)=[O:29])[CH2:10]2)=[CH:5][CH:4]=1

Participants

5

Reactant 2

HCID 15297071(2S,4S)-4-(4-methoxybenzyl)thio-1-(4-nitrobenzyloxycarbonyl)-L-prolineHCID 86752001HCID 86752001, compound

Product 1

HCID 10771163HCID 10771163, compoundYield 58.8%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 81531DiisopropylethylamineSolvent

Procedure

3.5 g of N,N'-carbonyldiimidazole were added to a solution of 8.0 g of (2S,4S)-4-(4-methoxybenzylthio)-1-(4-nitrobenzyloxycarbonyl)-2-pyrrolidinecarboxylic acid in 80 ml of dry acetonitrile, and the resulting mixture was stirred at room temperature for 30 minutes. A solution of 14.0 g of 1-(4-nitrobenzyloxycarbonylmethyl)homopiperazine bis(trifluoroacetate) in 80 ml of dry acetonitrile and 14.1 ml of diisopropylethylamine were added, whilst ice-cooling, to the mixture, and the resulting mixture was stirred at room temperature for 1.5 hours and then at 30° C. for a further 1.5 hours after which it was allowed to stand overnight at room temperature. At the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure, and the resulting residue was diluted with ethyl acetate. The dilute solution was washed with water and with an aqueous solution of sodium chloride, in that order, and it was then dried over anhydrous magnesium sulfate. The solvent was then removed by distillation under reduced pressure, and the resulting residue was purified by column chromatography through silica gel (Merck Art 9385), using ethyl acetate as the eluent, to give 7.6 g of the title compound as an amorphous solid.

Workup

  1. temperaturecooling, to the mixture
  2. stirringthe resulting mixture was stirred at room temperature for 1.5 hours
  3. waitat 30° C. for a further 1.5 hours after which it was allowed
  4. waitto stand overnight at room temperature
  5. concentrationAt the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure
  6. additionthe resulting residue was diluted with ethyl acetate
  7. washThe dilute solution was washed with water and with an aqueous solution of sodium chloride, in that order, and it
  8. dry with materialwas then dried over anhydrous magnesium sulfate
  9. customThe solvent was then removed by distillation under reduced pressure
  10. customthe resulting residue was purified by column chromatography through silica gel (Merck Art 9385)

Sources & evidence

ORD record
ord-ea055dc993ee485593d1cdc9ec41cd75
Source dataset
uspto-grants-1999_02
Patent number
US05866564

Reaction notes

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