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

HRID 2231532Notes

Reaction equation

HRID 2231532 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][CH3:32])[NH:29][C:28]1=[O:33].C1OC1C>C(Cl)Cl.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][CH3:32])[NH:29][C:28]2=[O:33])=[O:22])[N:18]=1)=[O:12]

Participants

8

Reactant 4

HCID 6378Propylene OxideHCID 10426DiphosgeneHCID 581157C8H8ClN3O4SHCID 54083832(3R,4S)-3-amino-4-methylthio-2-oxoazetidine

Product 1

HCID 54560850(3R,4S)-3-[2-(2-chloroacetamidothiazol-4-yl)-2-methoxyiminoacetamido]-4-methylthio-2-oxoazetidine

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent2×

Procedure

To a solution of 0.228 g of DMF in 5 ml of methylene chloride is added at -10° C. 0.137 ml of diphosgene. The mixture is then stirred for 30 minutes at room temperature, to which is added at a temperature of -70° C. 15 ml of methylene chloride solution containing 0.80 g of 2-(2-chloroacetamidothiazol-4-yl)-2-methyoxyiminoacetic acid and 0.316 g of triethylamine. The mixture is stirred for two hours at -25° C., then cooled to -70° C., followed by addition of 0.632 g of triethyl amine, 0.69 g of tosyl salt of (3R,4S)-3-amino-4-methylthio-2-oxoazetidine and 2 ml of propylene oxide. The temperature of the mixture is raised up to 0° C. in the course of one hour, while stirring. The mixture is stirred for further two hours at the same temperature, then concentrated, followed by addition of THF and removal of the resulting insolubles by filtration. The filtrate is concentrated and the residue is purified on a silica-gel column (AcOEt:CHCl3 :CH3OH=3:3:1) to yield 0.461 g of (3R,4S)-3-[2-(2-chloroacetamidothiazol-4-yl)-2-methoxyiminoacetamido]-4-methylthio-2-oxoazetidine.

Workup

  1. additionis added at a temperature of -70° C
  2. stirringThe mixture is stirred for two hours at -25° C.
  3. temperaturecooled to -70° C.
  4. temperatureThe temperature of the mixture is raised up to 0° C. in the course of one hour
  5. stirringwhile stirring
  6. stirringThe mixture is stirred for further two hours at the same temperature
  7. concentrationconcentrated
  8. additionfollowed by addition of THF and removal of the resulting insolubles by filtration
  9. concentrationThe filtrate is concentrated
  10. customthe residue is purified on a silica-gel column (AcOEt:CHCl3 :CH3OH=3:3:1)

Sources & evidence

ORD record
ord-c04cb894f8ab48f1b53524ff556d095d
Source dataset
uspto-grants-1988_11
Patent number
US04782147

Reaction notes

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