Diisopropylethylamine → (2S, 4S)-2-[3-(1-Imidazolyl)azetidin-1-ylcarbonyl]-4-(4-methoxybenzylthio)-1-(4-nitrobenzyloxycarbonyl)pyrrolidine

HRID 362119Notes

Reaction equation

HRID 362119 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](O)=[O:28])[CH2:10]2)=[CH:5][CH:4]=1.Cl.Cl.[N:34]1([CH:39]2[CH2:42][NH:41][CH2:40]2)[CH:38]=[CH:37][N:36]=[CH:35]1.C(N(C(C)C)CC)(C)C>C(#N)C.CO>[N:34]1([CH:39]2[CH2:42][N:41]([C:27]([C@@H:11]3[CH2:10][C@H:9]([S:8][CH2:7][C:6]4[CH:30]=[CH:31][C:3]([O:2][CH3:1])=[CH:4][CH:5]=4)[CH2:13][N:12]3[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])=[O:28])[CH2:40]2)[CH:38]=[CH:37][N:36]=[CH:35]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 15297071(2S,4S)-4-(4-methoxybenzyl)thio-1-(4-nitrobenzyloxycarbonyl)-L-prolineHCID 54593362153836-44-3

Product 1

HCID 67881964(2S, 4S)-2-[3-(1-Imidazolyl)azetidin-1-ylcarbonyl]-4-(4-methoxybenzylthio)-1-(4-nitrobenzyloxycarbonyl)pyrrolidineYield 85.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent2×

Conditions

Temperature
40 °C

Procedure

3.80 g of (2S, 4S)-4-(4-methoxybenzylthio)-1-(4-nitrobenzyloxycarbonyl)-2-pyrrolidinecarboxylic acid were dissolved in 40 ml of dry acetonitrile. 1.65 g of N,N'-carbonyldiimidazole were added to the resulting solution, and the mixture was stirred at 40° C. for 1 hour. A solution of 2.00 g of 3-(1-imidazolyl)azetidine dihydrochloride [prepared as described in step (b) above] and 2.90 g of diisopropylethylamine dissolved in a mixture of 30 ml of dry acetonitrile and 5 ml of methanol was then added at room temperature to the reaction mixture, after which the mixture was stirred at the same temperature for 1 hour. 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 with water and with an aqueous solution of sodium chloride, in that order. The ethyl acetate layer was separated, dried over anhydrous magnesium sulfate and concentrated by evaporation under reduced pressure. The resulting residue was subjected to silica gel chromatography to obtain 4.00 g of the title compound, as a powder, from the fraction obtained by elution with an 85:15 by volume mixture of ethyl acetate and methanol.

Workup

  1. additionwas then added at room temperature to the reaction mixture
  2. stirringafter which the mixture was stirred at the same temperature for 1 hour
  3. concentrationAt the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure
  4. additionthe residue was diluted with ethyl acetate
  5. washThe diluted solution was washed with water and with an aqueous solution of sodium chloride, in that order
  6. customThe ethyl acetate layer was separated
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated by evaporation under reduced pressure

Sources & evidence

ORD record
ord-0696eefc04dc43109aae9e5a82972590
Source dataset
uspto-grants-1999_02
Patent number
US05866564

Reaction notes

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