Diisopropylethylamine → (2S,4S)-2-(3-Aminoazetidin-1-ylcarbonyl)-4-(4-methoxybenzylthio)-1-(4-nitrobenzyloxycarbonyl)pyrrolidine

HRID 362106Notes

Reaction equation

HRID 362106 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.[NH2:34][CH:35]1[CH2:38][NH:37][CH2:36]1.C(N(C(C)C)CC)(C)C>C(#N)C.CO>[NH2:34][CH:35]1[CH2:38][N:37]([C:27]([C@@H:11]2[CH2:10][C@H:9]([S:8][CH2:7][C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:31][CH:30]=3)[CH2:13][N:12]2[C:14]([O:16][CH2:17][C:18]2[CH:19]=[CH:20][C:21]([N+:24]([O-:26])=[O:25])=[CH:22][CH:23]=2)=[O:15])=[O:28])[CH2:36]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 13491919Azetidin-3-amine--hydrogen chloride (1/2)HCID 15297071(2S,4S)-4-(4-methoxybenzyl)thio-1-(4-nitrobenzyloxycarbonyl)-L-proline

Product 1

HCID 11145523(2S,4S)-2-(3-Aminoazetidin-1-ylcarbonyl)-4-(4-methoxybenzylthio)-1-(4-nitrobenzyloxycarbonyl)pyrrolidineYield 111.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
40 °C

Procedure

2.05 g of (2S, 4S)-4-(4-methoxybenzylthio)-1-(4-nitrobenzyloxycarbonyl)-2-pyrrolidine carboxylic acid were dissolved in 20 ml of dry acetonitrile, and 0.78 g of N,N'-carbonyldiimidazole was added to the resulting solution, after which the mixture was stirred at 40° C. for 1 hour. The resulting mixture was then added dropwise to a solution of 1.00 g of 3-aminoazetidine dihydrochloride and 2.40 ml of diisopropylethylamine in 10 ml of methanol, whilst ice-cooling, and the mixture was stirred at the same temperature for 1 hour. At the end of this time, the reaction mixture was filtered, and the filtrate was concentrated by evaporation under reduced pressure. The resulting residue was diluted with ethyl acetate and washed with water and with an aqueous solution of sodium chloride, in that order. The ethyl acetate layer was dried over anhydrous magnesium sulfate and concentrated by evaporation under reduced pressure. The residue was subjected to silica gel column chromatography (silica gel 60 9385, manufactured by Merck, 100 g) to give 2.56 g of the title compound, in the form of an amorphous powder, from the fraction obtained by elution with a 65:35 by volume mixture of ethyl acetate and methanol.

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred at the same temperature for 1 hour
  3. filtrationAt the end of this time, the reaction mixture was filtered
  4. concentrationthe filtrate was concentrated by evaporation under reduced pressure
  5. additionThe resulting residue was diluted with ethyl acetate
  6. washwashed with water and with an aqueous solution of sodium chloride, in that order
  7. dry with materialThe ethyl acetate layer was dried over anhydrous magnesium sulfate
  8. concentrationconcentrated by evaporation under reduced pressure

Sources & evidence

ORD record
ord-898be453c9f7488c8e14f2b72130963a
Source dataset
uspto-grants-1999_02
Patent number
US05866564

Reaction notes

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