Water → HCID 68227654, compound

HRID 239089Notes

Reaction equation

HRID 239089 reaction equation
C(O)(=O)CC(CC(O)=O)(C(O)=O)[OH:4].N[C@@:15]1(C#N)[C@H:20]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([Cl:30])[CH:24]=2)[CH2:19][C@@H:18]2[C@H:16]1[C@@:17]2([F:34])[C:31]([NH2:33])=[O:32].C(O)(=O)CC(CC(O)=O)(C(O)=O)O.N[C@]1(C#N)[C@H](OCC2C=CC(Cl)=C(Cl)C=2)C[C@@H]2[C@H]1[C@@]2(F)C(N)=O.O.C(OCC)(=O)C>CO.C(Cl)(Cl)Cl>[Cl:30][C:25]1[CH:24]=[C:23]([CH:28]=[CH:27][C:26]=1[Cl:29])[CH2:22][O:21][C@@H:20]1[CH2:19][C@@H:18]2[C@@H:16]([C@@:17]2([F:34])[C:31]([NH2:33])=[O:32])[C:15]1=[O:4]

Participants

7

Reactant 4

HCID 962Water2×HCID 8857Ethyl AcetateHCID 68227671HCID 68227671, compoundHCID 68227954HCID 68227954, compound

Product 1

HCID 68227654HCID 68227654, compoundYield 977.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6212ChloroformSolvent

Conditions

Temperature
91.5 °C

Procedure

174.84 g [containing 0.351 g of (1R,2S,3R,5R,6R)-2-amino-2-cyano-3-[(3,4-dichloro benzyl)oxy]-6-fluoro bicyclo[3.1.0]hexane-6-carboxamide citrate (6b) and 3.853 g of (1R,2R,3R,5R,6R)-2-amino-2-cyano-3-[(3,4-dichloro benzyl)oxy]-6-fluorobicyclo[3.1.0]hexane-6-carboxamide citrate (8b)] of the 190.36 g of the filtrate and washing solution (acetic acid solution) obtained from the Example 9 was added with 174 mL of water and stirred for 4.5 hrs under heating at 90 to 93° C. The reaction solution was cooled to room temperature, added with ethyl acetate and water, and extracted. The organic layer was washed with water, a saturated aqueous solution of sodium hydrogen carbonate, and a saturated aqueous solution of sodium chloride in order, and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure to give a crude product, which was then subjected to silica gel column chromatography (eluent solution: chloroform:methanol=20:1). The concentrated residues obtained were crystallized with chloroform-hexane to obtain 2.07 g of (1R,3R,5R,6R)-3-[(3,4-dichloro benzyl)oxy]-6-fluoro-2-oxo bicyclo[3.1.0]hexane-6-carboxamide (5b) as a colorless solid.

Workup

  1. washwashing solution (acetic acid solution)
  2. customobtained from the Example 9
  3. temperatureThe reaction solution was cooled to room temperature
  4. extractionextracted
  5. washThe organic layer was washed with water
  6. dry with materiala saturated aqueous solution of sodium hydrogen carbonate, and a saturated aqueous solution of sodium chloride in order, and dried over anhydrous magnesium sulfate
  7. customThe solvent was removed by distillation under reduced pressure
  8. customto give a crude product, which
  9. customThe concentrated residues obtained
  10. customwere crystallized with chloroform-hexane

Sources & evidence

ORD record
ord-1ec872ec8fff4ae2b22a715216a91ce1
Source dataset
uspto-grants-2014_02
Patent number
US08642777B2

Reaction notes

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