Acetic Acid → Acivicin

HRID 1263096Notes

Reaction equation

HRID 1263096 reaction equation
[Cl:1][C:2]1[CH2:6][CH:5]([CH:7]([N:11]2C(=O)C3=CC=CC=C3C2=O)[C:8]([OH:10])=[O:9])[O:4][N:3]=1.O.NN.C(O)(=O)C>O>[NH2:11][C@@H:7]([C@H:5]1[O:4][N:3]=[C:2]([Cl:1])[CH2:6]1)[C:8]([OH:10])=[O:9]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 24654Hydrazine hydrate (1:1)HCID 3323672-(3-chloro-4,5-dihydro-1,2-oxazol-5-yl)-2-(1,3-dioxoisoindol-2-yl)acetic acid

Product 1

HCID 294641AcivicinYield 58.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To 710 mg (2.3 mmole) of 3-chloro-4,5-dihydro-α-phthalimido-5-isoxazole acetic acid in 15 ml of water is added 260 μl of hydrazine hydrate and the solution stirred at 50° for 7 hours. After cooling, the solution is adjusted to pH 5.5 with acetic acid (80 μl), filtered, and the precipitate washed with 13 ml water. The filtrate is diluted with 200 ml of 2-butanol and allowed to crystallized in the refrigerator for 18 hours. Filtration yielded 240 mg of (αS,5S)-α-amino-3-chloro-4,5-dihydro-5-isoxazole acetic acid; concentrating the mother liquors approximately 15% afforded 50 mg of a second crop of (αS,5S)-α-amino-3-chloro-4,5-dihydro-5-isoxazole acetic acid (71%). Tlc: Rf 0.40 (60/20/15/5; MEK/Acet/H2O/AcOH).

Workup

  1. temperatureAfter cooling
  2. filtrationfiltered
  3. washthe precipitate washed with 13 ml water
  4. additionThe filtrate is diluted with 200 ml of 2-butanol
  5. customto crystallized in the refrigerator for 18 hours
  6. filtrationFiltration

Sources & evidence

ORD record
ord-7bfc38476db6482b9e9bcd93441cd6ff
Source dataset
uspto-grants-1984_06
Patent number
US04455430

Reaction notes

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