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 1781185Notes

Reaction equation

HRID 1781185 reaction equation
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]

Participants

8

Reactant 6

HCID 807IodineHCID 78391,2-Dibromoethane2×HCID 5462224MagnesiumHCID 103380523-(2-Bromopropanoyl)spiro[benzo[e][1,3]oxazine-2,1'-cyclohexan]-4(3H)-oneHCID 10935078AzetidonHCID 21905121Ammonium hydrochloride

Product 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-oneYield 80.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
5 °C

Procedure

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 get column chromatography (solvent; hexane:ethyl acetate=6:1-3:1) to obtain 1.61 g of 3-{(2R)-2-[(3S,4R)-3-[(1R)-l-t-butyldimethylsilyloxyethyl]-2-oxoazetidin-4-yl]propionyl}-spiro[2,3-dihydro-4H-1,3-benzoxazine-2,1'-cyclohexan]-4-one.

Workup

  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
  12. customget column chromatography (solvent; hexane:ethyl acetate=6:1-3:1)

Sources & evidence

ORD record
ord-3fb4f783a47b4440a5964fe51d2b85da
Source dataset
uspto-grants-1997_05
Patent number
US05631363

Reaction notes

Loading…