1-(2-Hydroxyethyl)piperazine → (2S,4R)-2-(4-(2-hydroxyethyl)-1-piperazinylcarbonyl)-4-trimethylsilyloxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine

HRID 37343Notes

Reaction equation

HRID 37343 reaction equation
[N+:1]([C:4]1[CH:26]=[CH:25][C:7]([CH2:8][O:9][C:10]([N:12]2[CH2:19][C@H:18]([O:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[CH2:17][C@H:13]2[C:14](O)=[O:15])=[O:11])=[CH:6][CH:5]=1)([O-:3])=[O:2].[OH:27][CH2:28][CH2:29][N:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1>C(#N)C>[OH:27][CH2:28][CH2:29][N:30]1[CH2:35][CH2:34][N:33]([C:14]([C@@H:13]2[CH2:17][C@@H:18]([O:20][Si:21]([CH3:23])([CH3:22])[CH3:24])[CH2:19][N:12]2[C:10]([O:9][CH2:8][C:7]2[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:26][CH:25]=2)=[O:11])=[O:15])[CH2:32][CH2:31]1

Participants

4

Reactant 2

HCID 76771-(2-Hydroxyethyl)piperazineHCID 22851545trans-1-(4-nitrobenzyloxycarbonyl)-4-trimethylsilyloxy-L-proline

Product 1

HCID 57135594(2S,4R)-2-(4-(2-hydroxyethyl)-1-piperazinylcarbonyl)-4-trimethylsilyloxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidineYield 65.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

674 mg of trans-1-(4-nitrobenzyloxycarbonyl)-4-trimethylsilyloxy-L-proline [prepared as described in step (2) above] were dissolved in 14 ml of anhydrous acetonitrile, and 343 mg of N,N'-carbonyldiimidazole were added to the resulting solution. The resulting mixture was then stirred at room temperature for 1 hour. At the end of this time, a solution of 275 mg of 1-(2-hydroxyethyl)piperazine in 1 ml of anhydrous acetonitrile was added to the reaction mixture, and the resulting mixture was stirred overnight at room temperature. It was then concentrated by evaporation under reduced pressure, and the resulting residue was mixed with an aqueous solution of sodium chloride and extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure, to give 574 mg of (2S,4R)-2-(4-(2-hydroxyethyl)-1-piperazinylcarbonyl)-4-trimethylsilyloxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine as an oil. The whole of this product was dissolved in 5.7 ml of methylene chloride, and 170 mg of 4-dimethylaminopyridine and 300 mg of 4-nitrobenzyl chloroformate were added to the resulting solution, whilst ice-cooling. The mixture was then stirred at room temperature for 1 hour, after which the solvent was removed by distillation under reduced pressure. The resulting residue was mixed with 15 ml of 1N aqueous hydrochloric acid and then stirred at room temperature for 1 hour. At the end of this time, the mixture was made mildly basic by the addition of an aqueous solution of sodium hydrogen-carbonate; it was then extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate; the solvent was then removed by distillation under reduced pressure, and the resulting residue was purified in a similar manner to that described in step (b) above, to afford 348 mg of the title compound. The infra-red absorption spectrum and nuclear magnetic resonance spectrum of the product thus obtained were identical with those of the compound prepared as described in step (a), above.

Workup

  1. stirringthe resulting mixture was stirred overnight at room temperature
  2. concentrationIt was then concentrated by evaporation under reduced pressure
  3. additionthe resulting residue was mixed with an aqueous solution of sodium chloride
  4. extractionextracted with ethyl acetate
  5. washThe extract was washed with water
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customThe solvent was removed by distillation under reduced pressure

Sources & evidence

ORD record
ord-bb16b55af40e41f7a0f571daabe149eb
Source dataset
uspto-grants-1995_05
Patent number
US05420119

Reaction notes

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