Water → HCID 57081076, compound

HRID 1378371Notes

Reaction equation

HRID 1378371 reaction equation
[C:1](=[O:4])([O-:3])[O-].[Na+].[Na+].[CH2:7](Br)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.O.[C:16]([O:19]CC)(=[O:18])[CH3:17].[CH3:22][N:23](C=O)C>CCCCCC>[CH2:7]([N:23]1[C@H:22]([C:1]([OH:3])=[O:4])[C@H:17]1[C:16]([OH:19])=[O:18])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

7

Reactant 5

HCID 962WaterHCID 6228DimethylformamideHCID 7498Benzyl BromideHCID 8857Ethyl AcetateHCID 10340Sodium Carbonate

Product 1

HCID 57081076HCID 57081076, compound

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Conditions

Temperature
60 °C

Procedure

Diethyl ester of (2S,3S)-aziridine-2,3-dicarboxylic acid (10.3 g) obtained in Working Example 42 was dissolved in DMF (155 ml). To the solution was added sodium carbonate (4.4 g) and benzyl bromide (14.1 g), and the mixture was stirred for 15 hours at 60° C. The reaction mixture was poured into ice-cooling water, which was subjected to extraction with ethyl acetate (100 ml×2). The ethyl acetate layer was washed with water and a saturated aqueous saline solution, which was dried over anhydrous sodium sulfate and subjected to a slica gel column chromatography. Elution was conducted with eluents prepared by adding ethyl acetate to hexane in sequence. The fractions eluted with 10% (v/v) ethyl acetate were combined and concentrated to dryness to give diethyl ester of (2S,3S)-N-benzylaziridine-2,3-dicarboxylic acid (12.3 g) as a colorless oily product (yield 81%). The whole amount of the product was dissolved in ethanol (300 ml). To the solution was added, under ice-cooling, 1N aqueous solution of sodium hydroxide (44 ml). The mixture was stirred for one hour and for further 30 minutes at room temperature. The reaction mixture was adjusted to pH7, to which was added water, and the mixture was concentrated. The concentrate was adjusted to pH7, followed by washing with ether. The aqueous layer was adjusted to pH 3, to which was added sodium chloride, followed by extraction with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous saline solution, dried over anhydrous sodium sulfate, followed by concentration to give monoethyl ester of (2S,3S)-N-benzylaziridine-2,3-dicarboxylic acid (2.0 g) as a white powdery product (yield 18%). The compound thus obtained (0.50 g) was condensed, in substantially the same manner as Working Example 8, with N-(L-phenylalanyl) benzylamine hydrochloride (0.64 g) obtained in Working Example 91 to give the above-titled compound (Compound 95; 0.91 g) as a white powdery product (yield 94%).

Workup

  1. additionThe reaction mixture was poured into ice-
  2. extractionwas subjected to extraction with ethyl acetate (100 ml×2)
  3. washThe ethyl acetate layer was washed with water
  4. dry with materiala saturated aqueous saline solution, which was dried over anhydrous sodium sulfate
  5. washElution
  6. customprepared
  7. washThe fractions eluted with 10% (v/v) ethyl acetate
  8. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-4cef27d395084fbd8b4fb124dd3afaf6
Source dataset
uspto-grants-1997_09
Patent number
US05668128

Reaction notes

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