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 849306Notes

Reaction equation

HRID 849306 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]-2-azetidinone, 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 0.2 M 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; hexane:ethyl acetate=3:1)

Sources & evidence

ORD record
ord-3cac3f46c0b24c6eb8d3857e82863fd2
Source dataset
uspto-grants-2000_01
Patent number
US06011150

Reaction notes

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