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

HRID 978840노트

반응식

HRID 978840 반응식
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]

참가 물질

8

반응물 4

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

생성물 1

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

시약·촉매·용매 3

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매2회HCID 8471Triethylamine용매2회

실험 절차

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-methoxyiminoacetic 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.

후처리

  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)

출처 및 근거

ORD 기록
ord-4cd4378907be41b3a03cb8bc1a6dd2a2
출처 데이터셋
uspto-grants-1987_05
특허 번호
US04665067

반응 노트

불러오는 중…