Imidazole → (3S,4R)-3-[(R)-1-hydroxyethyl]-4-[(R)-1-methyl-3-allyloxycarbonyl-2-oxopropyl]-2-azetidinone

HRID 1461491Notes

Reaction equation

HRID 1461491 reaction equation
[O-]CC.[Mg+2].[O-]CC.[C:8]([O:14][CH2:15][CH:16]=[CH2:17])(=[O:13])[CH2:9][C:10]([OH:12])=O.[OH:18][C@@H:19]([C@@H:21]1[C@@H:24]([C@@H:25](C)[C:26](=O)N2CCSC2=S)[NH:23][C:22]1=[O:35])[CH3:20].N1C=CN=C1>O1CCCC1>[OH:18][C@@H:19]([C@H:21]1[C:22](=[O:35])[NH:23][C@@H:24]1[C@@H:25]([CH3:26])[C:10](=[O:12])[CH2:9][C:8]([O:14][CH2:15][CH:16]=[CH2:17])=[O:13])[CH3:20]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 164963Magnesium ethanolateHCID 10888030Malonic acid monoallyl esterHCID 14699456(3S,4R)-3-[(1R)-1-hydroxyethyl]-4-[(1R)-1-methyl-2-oxo-2-(2-thioxothiazolidin-3-yl)ethyl]-2-azetidinone

Product 1

HCID 14329059(3S,4R)-3-[(R)-1-hydroxyethyl]-4-[(R)-1-methyl-3-allyloxycarbonyl-2-oxopropyl]-2-azetidinoneYield 84.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred suspension of magnesium ethoxide (14.7 g) in tetrahydrofuran (250 ml) was added allyl hydrogen malonate (38.8 g) at 30° C. under nitrogen atmosphere. The resultant mixture was stirred at ambient temperature for 10 hours. To this mixture were added (3S,4R)-3-[(1R)-1-hydroxyethyl]-4-[(1R)-1-methyl-2-oxo-2-(2-thioxothiazolidin-3-yl)ethyl]-2-azetidinone (24.7 g) and imidazole (8.8 g), and the mixture was allowed to heat to 60° C. for 1 hour. After evaporation of the solvent in vacuo, the residue was taken up into a mixture of ethyl acetate (300 ml) and brine (200 ml). After adjusting to pH 3.5 with concentrated hydrochloric acid at 5° C., the organic layer was separated and diluted with brine (200 ml). After adjusting to pH 8 with 30% aqueous potassium carbonate at 5° C., the organic layer was separated, washed with brine, dried over magnesium sulfate and evaporated in vacuo. The residue was chromatographed on silica gel (600 ml) eluting with a mixture of dichloromethane and acetone (19:1-1:1 v/v) to give allyl (4R)-4-[(2R,3S)-3-{(1R)-1-hydroxyethyl}-4-oxoazetidin-2-yl]-3-oxopentanoate (19.46 g).

Workup

  1. customAfter evaporation of the solvent in vacuo
  2. additionthe residue was taken up into a mixture of ethyl acetate (300 ml) and brine (200 ml)
  3. customAfter adjusting to pH 3.5 with concentrated hydrochloric acid at 5° C.
  4. customthe organic layer was separated
  5. additiondiluted with brine (200 ml)
  6. customAfter adjusting to pH 8 with 30% aqueous potassium carbonate at 5° C.
  7. customthe organic layer was separated
  8. washwashed with brine
  9. dry with materialdried over magnesium sulfate
  10. customevaporated in vacuo
  11. customThe residue was chromatographed on silica gel (600 ml)
  12. washeluting with a mixture of dichloromethane and acetone (19:1-1:1 v/v)

Sources & evidence

ORD record
ord-20b70cbfde6245e89f89d954febfa536
Source dataset
uspto-grants-1991_12
Patent number
US05075437

Reaction notes

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