Iodine → 3-[(2R)-2-[(3S,4R)-3-[(1R)-1-t-butyldimethylsilyloxyethyl]-2-oxoazetidin-4-yl]propionyl}-spiro[2,3-dihydro-4H-1,3-benzoxazine-2,1'-cyclohexan]-4-one

HRID 849309노트

반응식

HRID 849309 반응식
II.[Mg].BrCCBr.C(O[C@H:12]1[NH:15][C:14](=[O:16])[C@@H:13]1[C@H:17]([O:19][Si:20]([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21])[CH3:18])(=O)C.Br[CH:28]([CH3:47])[C:29]([N:31]1[C:36]2([CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]2)[O:35][C:34]2[CH:42]=[CH:43][CH:44]=[CH:45][C:33]=2[C:32]1=[O:46])=[O:30].Cl.[NH4+]>O1CCCC1>[Si:20]([O:19][C@@H:17]([C@@H:13]1[C@@H:12]([C@@H:28]([CH3:47])[C:29]([N:31]2[C:36]3([CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]3)[O:35][C:34]3[CH:42]=[CH:43][CH:44]=[CH:45][C:33]=3[C:32]2=[O:46])=[O:30])[NH:15][C:14]1=[O:16])[CH3:18])([C:23]([CH3:24])([CH3:25])[CH3:26])([CH3:21])[CH3:22]

참가 물질

8

반응물 6

HCID 807IodineHCID 78391,2-Dibromoethane2회HCID 5462224MagnesiumHCID 103380523-(2-Bromopropanoyl)spiro[benzo[e][1,3]oxazine-2,1'-cyclohexan]-4(3H)-oneHCID 10935078AzetidonHCID 21905121Ammonium hydrochloride

생성물 1

HCID 103458983-[(2R)-2-[(3S,4R)-3-[(1R)-1-t-butyldimethylsilyloxyethyl]-2-oxoazetidin-4-yl]propionyl}-spiro[2,3-dihydro-4H-1,3-benzoxazine-2,1'-cyclohexan]-4-one수율 80.4%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매3회

반응 조건

온도
5 °C

실험 절차

A mixture of 10 ml of tetrahydrofuran and a small amount of iodine is added to 437 mg of magnesium piece at a room temperature and 0.75 g of 1,2-dibromoethane are added dropwise thereto with stirring. When the exothermic reaction starts and the mixture begins to reflux, a solution of 1.51 g of 1,2-dibromoethane in 3 ml of tetrahydrofuran is added dropwise thereto. Then, the mixture is refluxed for 30 minutes. The mixture is cooled to a temperature of 5° C. and to this cooled liquid is added dropwise a mixture of 1.15 g of (3R,4R)-4-acetoxy-3-[(1R)-1-t-butyldimethylsilyloxyethyl]-2-azetidinone and 2.11 g of 3-(2-bromopropionyl)-spiro[2,3-dihydro-4H-1,3-benzoxazine-2,1'-cyclohexan]-4-one in 5 ml of tetrahydrofuran. Then, the mixture is stirred at 10° C. for one hour. 60 ml of aqueous saturated ammonium hydrochloride are added thereto and the mixture is extracted with ethyl acetate. The extract is washed, dried and evaporated to remove the solvent. The residue is purified by silica gel column chromatography (solvent; hexane:ethyl acetate=6:1-3:1) to obtain 1.61 g of 3-{(2R)-2-[(3S,4R)-3-[(1R)-1-t-butyldimethylsilyloxyethyl]-2-oxoazetidin-4-yl]propionyl}-spiro[2,3-dihydro-4H-1,3-benzoxazine-2,1'-cyclohexan]-4-one.

후처리

  1. customWhen the exothermic reaction starts
  2. temperatureto reflux
  3. temperatureThen, the mixture is refluxed for 30 minutes
  4. additionis added dropwise
  5. stirringThen, the mixture is stirred at 10° C. for one hour
  6. extractionthe mixture is extracted with ethyl acetate
  7. washThe extract is washed
  8. customdried
  9. customevaporated
  10. customto remove the solvent
  11. customThe residue is purified by silica gel column chromatography (solvent; hexane:ethyl acetate=6:1-3:1)

출처 및 근거

ORD 기록
ord-d9acd1945d3a4523986b9b2d9507fcbe
출처 데이터셋
uspto-grants-2000_01
특허 번호
US06011150

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