Acetonitrile → HCID 86753693, compound

HRID 362022Notes

Reaction equation

HRID 362022 reaction equation
C([N:3]([CH2:6][CH3:7])[CH2:4][CH3:5])C.[C:8](Cl)(=[O:13])[C:9](C)(C)C.[CH3:15][O:16][C:17]1[CH:45]=[CH:44][C:20]([CH2:21][S:22][C@@H:23]2[CH2:27][N:26]([C:28]([O:30][CH2:31][C:32]3[CH:37]=[CH:36][C:35]([N+:38]([O-:40])=[O:39])=[CH:34][CH:33]=3)=[O:29])[C@H:25]([C:41](O)=[O:42])[CH2:24]2)=[CH:19][CH:18]=1.[C:46]([O:50]C(N1CCNC(C)C1)=O)([CH3:49])([CH3:48])[CH3:47].C(#[N:62])C>O1CCCC1>[CH3:15][O:16][C:17]1[CH:45]=[CH:44][C:20]([CH2:21][S:22][C@@H:23]2[CH2:27][N:26]([C:28]([O:30][CH2:31][C:32]3[CH:33]=[CH:34][C:35]([N+:38]([O-:40])=[O:39])=[CH:36][CH:37]=3)=[O:29])[C@H:25]([C:41]([N:3]3[CH2:4][CH2:5][N:62]([O:50][C:46]([CH3:47])([CH3:48])[CH3:49])[C:9](=[C:8]=[O:13])[CH:6]3[CH3:7])=[O:42])[CH2:24]2)=[CH:19][CH:18]=1

Participants

7

Reactant 5

HCID 6342AcetonitrileHCID 8471TriethylamineHCID 62493Pivaloyl chlorideHCID 2756810tert-Butyl 3-methylpiperazine-1-carboxylateHCID 15297071(2S,4S)-4-(4-methoxybenzyl)thio-1-(4-nitrobenzyloxycarbonyl)-L-proline

Product 1

HCID 86753693HCID 86753693, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3.41 ml of triethylamine and 3.03 ml of pivaloyl chloride were added dropwise to a solution of 9.99 g of (2S,4S)-4-(4-methoxybenzylthio)-1-(4-nitrobenzyloxy-carbonyl)-2-pyrrolidinecarboxylic acid in 100 ml of dry acetonitrile, whilst ice-cooling, and the resulting mixture was stirred at the same temperature for 20 minutes. A solution of 5.38 g of 1-t-butoxycarbonyl-3-methylpiperazine in 50 ml of dry tetrahydrofuran was then added dropwise to the mixture, and the mixture was stirred at the same temperature for 30 minutes and then at room temperature for 2 hours. At the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure, and the residue was diluted with ethyl acetate. The diluted solution was washed, in turn, with a 1N aqueous solution of oxalic acid, with water and with an aqueous solution of sodium chloride. The ethyl acetate solution was dried over anhydrous magnesium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was purified by column chromatography through silica gel, using a gradient elution method, with mixtures of ethyl acetate and cyclcohexane ranging from 1:1 to 3:2 by volume as the eluent, to give 8.56 g of the title compound, as an amorphous solid.

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred at the same temperature for 30 minutes
  3. waitat room temperature for 2 hours
  4. concentrationAt the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure
  5. additionthe residue was diluted with ethyl acetate
  6. washThe diluted solution was washed, in turn, with a 1N aqueous solution of oxalic acid, with water and with an aqueous solution of sodium chloride
  7. dry with materialThe ethyl acetate solution was dried over anhydrous magnesium sulfate
  8. customthe solvent was removed by distillation under reduced pressure
  9. customThe residue was purified by column chromatography through silica gel
  10. washa gradient elution method

Sources & evidence

ORD record
ord-7ed6c3ed58354b609bdc5ea99e1c6550
Source dataset
uspto-grants-1999_02
Patent number
US05866564

Reaction notes

Loading…