Phosphate → 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 1756882Notes

Reaction equation

HRID 1756882 reaction equation
C(O[C@H:5]1[NH:8][C:7](=[O:9])[C@@H:6]1[C@H:10]([O:12][Si:13]([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14])[CH3:11])(=O)C.Br[CH:21]([CH3:40])[C:22]([N:24]1[C:29]2([CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]2)[O:28][C:27]2[CH:35]=[CH:36][CH:37]=[CH:38][C:26]=2[C:25]1=[O:39])=[O:23].P([O-])([O-])([O-])=O>[Zn].O1CCCC1>[Si:13]([O:12][C@@H:10]([C@@H:6]1[C@@H:5]([C@@H:21]([CH3:40])[C:22]([N:24]2[C:29]3([CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]3)[O:28][C:27]3[CH:35]=[CH:36][CH:37]=[CH:38][C:26]=3[C:25]2=[O:39])=[O:23])[NH:8][C:7]1=[O:9])[CH3:11])([C:16]([CH3:17])([CH3:18])[CH3:19])([CH3:14])[CH3:15]

Participants

6

Reactant 3

HCID 1061PhosphateHCID 103380523-(2-Bromopropanoyl)spiro[benzo[e][1,3]oxazine-2,1'-cyclohexan]-4(3H)-oneHCID 10935078Azetidon

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 74.6%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent

Procedure

1.0 g of (3R, 4R)-4-acetoxy-3-[(1R)-1-t-butyldimethylsilyloxyethyl]-2azetidinone, 1.8 g of 3-(2-bromopropionyl)-spiro[2,3-dihydro-4H-1,3-benzoxazine-2,1'-cyclohexan]-4-one and 0.68 g of zinc powders are added to 15 ml of tetrahydrofuran and the mixture is refluxed for 30 minutes. After cooling, the reaction mixture is poured into 0.2M phosphate buffer (pH 7.0) and the mixture is extracted with methylene chloride. The extract is washed, dried and evaporated to remove the solvent. The residue is purified by silica gel column chromatography (solvent; hexane:ethyl acetate =3:1)to obtain 1.3 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.

Workup

  1. temperaturethe mixture is refluxed for 30 minutes
  2. temperatureAfter cooling
  3. extractionthe mixture is extracted with methylene chloride
  4. washThe extract is washed
  5. customdried
  6. customevaporated
  7. customto remove the solvent
  8. customThe residue is purified by silica gel column chromatography (solvent

Sources & evidence

ORD record
ord-583a1aed35724677ba677190b283c941
Source dataset
uspto-grants-1995_08
Patent number
US05442055

Reaction notes

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