Propylene Oxide → (3R,4R)-3-[2-(2-chloroacetamidothiazol-4-yl)-2-methoxyiminoacetamido]-4-methylsulfonyl-2-oxoazetidine

HRID 465190Notes

Reaction equation

HRID 465190 reaction equation
O=C(Cl)OC(Cl)(Cl)Cl.[Cl:9][CH2:10][C:11]([NH:13][C:14]1[S:15][CH:16]=[C:17]([C:19](=[N:23][O:24][CH3:25])[C:20]([OH:22])=O)[N:18]=1)=[O:12].[NH2:26][C@H:27]1[C@@H:30]([S:31]([CH3:34])(=[O:33])=[O:32])[NH:29][C:28]1=[O:35].C1OC1C>C(Cl)Cl.CC(N(C)C)=O.C(N(CC)CC)C.CN(C=O)C>[Cl:9][CH2:10][C:11]([NH:13][C:14]1[S:15][CH:16]=[C:17]([C:19](=[N:23][O:24][CH3:25])[C:20]([NH:26][C@H:27]2[C@@H:30]([S:31]([CH3:34])(=[O:33])=[O:32])[NH:29][C:28]2=[O:35])=[O:22])[N:18]=1)=[O:12]

Participants

9

Reactant 4

HCID 6378Propylene OxideHCID 10426DiphosgeneHCID 581157C8H8ClN3O4SHCID 53637648(3R,4R)-3-amino-4-methylsulfonyl-2-oxoazetidine

Product 1

HCID 53860321(3R,4R)-3-[2-(2-chloroacetamidothiazol-4-yl)-2-methoxyiminoacetamido]-4-methylsulfonyl-2-oxoazetidineYield 70.2%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent2×HCID 31374DimethylacetamideSolvent

Procedure

To a solution of 0.122 g of DMF in 5 ml of methylene chloride is added 0.10 ml of diphosgene at -10° C. The mixture is stirred for 30 minutes at room temperature, then cooled to a temperature of -70° C., followed by dropwise addition of 10 ml of methylene chloride solution containing 0.427 g of 2-(2-chloroacetamidothiazol-4-yl)-2-methoxyiminoacetic acid and 0.17 g of triethylamine. The mixture is stirred for 2 hours at a temperature ranging from -25° to -20° C., which is cooled to a temperature of -70° C., to which are added 0.17 g of triethylamine, a solution of 0.229 g of (3R,4R)-3-amino-4-methylsulfonyl-2-oxoazetidine in 3 ml of DMA, and 2 ml of propylene oxide, successively. The temperature of the mixture is raised up to room temperature in the course of 1.5 hours. The reaction mixture is concentrated under reduced pressure, and the residue is purified on a silica-gel column (ethyl acetate: n-hexane=1:1) to give 0.415 g of (3R,4R)-3-[2-(2-chloroacetamidothiazol-4-yl)-2-methoxyiminoacetamido]-4-methylsulfonyl-2-oxoazetidine. This is in agreement with the compound (syn-isomer) obtained in Reference Example 15B in IR and NMR.

Workup

  1. temperaturecooled to a temperature of -70° C.
  2. stirringThe mixture is stirred for 2 hours at a temperature
  3. customranging from -25° to -20° C.
  4. temperaturewhich is cooled to a temperature of -70° C., to which
  5. temperatureThe temperature of the mixture is raised up to room temperature in the course of 1.5 hours
  6. concentrationThe reaction mixture is concentrated under reduced pressure
  7. customthe residue is purified on a silica-gel column (ethyl acetate: n-hexane=1:1)

Sources & evidence

ORD record
ord-06844d6b447e4491a77549fd27bc7e37
Source dataset
uspto-grants-1985_10
Patent number
US04550105

Reaction notes

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