Citric Acid → 3-{(2R)-2-[(3S,4R)-3-[(1R)-1-t-butyldimethylsilyloxyethyl]-2-oxoazetidin-4-yl)propionyl}-(3aS-cis)-3,3a,8,8a-tetrahydro-2H-indeno[1,2-d]oxazol-2-one

HRID 1250994Notes

Reaction equation

HRID 1250994 reaction equation
[C:1]([N:5]1[C@H:9]2[C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:15]=3[CH2:16][C@H:8]2[O:7][C:6]1=[O:17])(=[O:4])[CH2:2][CH3:3].C([Mg]Cl)(C)(C)C.C(O[C@H:28]1[NH:31][C:30](=[O:32])[C@@H:29]1[C@H:33]([O:35][Si:36]([C:39]([CH3:42])([CH3:41])[CH3:40])([CH3:38])[CH3:37])[CH3:34])(=O)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1.C(OCC)(=O)C>[Si:36]([O:35][C@@H:33]([C@@H:29]1[C@@H:28]([C@@H:2]([CH3:3])[C:1]([N:5]2[C@H:9]3[C:10]4[CH:11]=[CH:12][CH:13]=[CH:14][C:15]=4[CH2:16][C@H:8]3[O:7][C:6]2=[O:17])=[O:4])[NH:31][C:30]1=[O:32])[CH3:34])([C:39]([CH3:40])([CH3:41])[CH3:42])([CH3:37])[CH3:38]

Participants

7

Reactant 4

HCID 311Citric AcidHCID 10935078AzetidonHCID 109663363-propionyl-(3aS-cis)-3,3a,8,8a-tetrahydro-2H-indeno[1,2-d]oxazol-2-oneHCID 178418310HCID 178418310, compound

Product 1

HCID 1317231003-{(2R)-2-[(3S,4R)-3-[(1R)-1-t-butyldimethylsilyloxyethyl]-2-oxoazetidin-4-yl)propionyl}-(3aS-cis)-3,3a,8,8a-tetrahydro-2H-indeno[1,2-d]oxazol-2-oneYield 67%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
5 °C

Procedure

Under a nitrogen atmosphere, 231 mg (1.0 mmol) of 3-propionyl-(3aS-cis)-3,3a,8,8a-tetrahydro-2H-indeno[1,2-d]oxazol-2-one was charged in a 30-ml three-necked flask to dissolve it in 2 ml of tetrahydrofuran. To the resulting solution, 2.75 ml (2.2 mmol) of a tetrahydrofuran solution (0.8M) of t-butylmagnesium chloride was slowly added dropwise at room temperature. After the resulting mixture was allowed to react for 20 minutes under the same conditions, the reaction mixture was cooled to 5° C. and added with 2 ml of a tetrahydrofuran solution of 287 mg (1.0 mmol) of (3R,4R)-4-acetoxy-3-[(R)-1-tert-butyldimethylsilyloxyethyl]azetidin-2-one at the same temperature. After stirring for 10 minutes, 10 ml of ethyl acetate was added to the reaction mixture, followed by the dropwise addition of 2 ml of a 10% aqueous solution of citric acid. After separation, the organic layer was washed with 2 ml of a saturated aqueous solution of sodium bicarbonate and 2 ml of a saturated aqueous solution of sodium cloride, dried over anhydrous magnesium sulfate and distilled to remove the solvent. The residue was purified by column chromatography, whereby 308 mg (0.67 mmol) of a condensation product was obtained (yield: 67%, β:α=95:5).

Workup

  1. customto react for 20 minutes under the same conditions
  2. customAfter separation
  3. washthe organic layer was washed with 2 ml of a saturated aqueous solution of sodium bicarbonate and 2 ml of a saturated aqueous solution of sodium cloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. distillationdistilled
  6. customto remove the solvent
  7. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-7d3907b6433e46c3a764f485555624ad
Source dataset
uspto-grants-2002_01
Patent number
US06340751B1

Reaction notes

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