Water → (1S,2S,3S,5R,6S)-3'-allyl 6-ethyl 3-fluoro-5'-oxospiro[bicyclo[3.1.0]hexan-2,4'-oxazolidine]-3',6-dicarboxylate

HRID 1486666Notes

Reaction equation

HRID 1486666 reaction equation
[CH2:1]([O:4][C:5]([N:7]1[C@:11]2([C@@H:16]([F:17])[CH2:15][C@@H:14]3[C@H:12]2[C@H:13]3[C:18]([OH:20])=[O:19])[C:10](=[O:21])[O:9][CH2:8]1)=[O:6])[CH:2]=[CH2:3].C(=O)([O-])[O-].[Cs+].[Cs+].S(C1C=CC(C)=CC=1)(O[CH2:32][CH3:33])(=O)=O.O>CN(C)C=O>[F:17][C@@H:16]1[C@@:11]2([C:10](=[O:21])[O:9][CH2:8][N:7]2[C:5]([O:4][CH2:1][CH:2]=[CH2:3])=[O:6])[C@H:12]2[C@H:14]([C@@H:13]2[C:18]([O:20][CH2:32][CH3:33])=[O:19])[CH2:15]1

Participants

6

Reactant 4

HCID 962WaterHCID 6638Ethyl p-methylbenzenesulfonateHCID 10796Cesium carbonateHCID 117987522(1S,2S,3S,5R,6S)-3'-((allyloxy)carbonyl)-3-fluoro-5'-oxospiro[bicyclo[3.1.0]hexan-2,4'-oxazolidine]-6-carboxylic acid

Product 1

HCID 117987721(1S,2S,3S,5R,6S)-3'-allyl 6-ethyl 3-fluoro-5'-oxospiro[bicyclo[3.1.0]hexan-2,4'-oxazolidine]-3',6-dicarboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of (1S,2S,3S,5R,6S)-3′-((allyloxy)carbonyl)-3-fluoro-5′-oxospiro[bicyclo[3.1.0]hexan-2,4′-oxazolidine]-6-carboxylic acid obtained below in Example A-1 (A-1-2, 200 mg) in N,N-dimethylformamide (6 mL), cesium carbonate (261 mg) was added, and the mixture was stirred at room temperature for 30 minutes. Ethyl tosylate (201 mg) was added and the mixture was stirred at room temperature for 1 hour. To the reaction mixture, water was added, and the mixture was extracted twice with ethyl acetate. The combined organic layer was washed once with water and once with brine, sequentially, and then the ethyl acetate layer was dried over anhydrous sodium sulfate. The insoluble was filtered off, the filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (silica gel cartridge, hexane:ethyl acetate=100:0-50:50) to give (1S,2S,3S,5R,6S)-3′-allyl 6-ethyl 3-fluoro-5′-oxospiro[bicyclo[3.1.0]hexan-2,4′-oxazolidine]-3′,6-dicarboxylate (Reference Example 1-1, 68 mg) as a colorless amorphous.

Workup

  1. stirringthe mixture was stirred at room temperature for 1 hour
  2. extractionthe mixture was extracted twice with ethyl acetate
  3. washThe combined organic layer was washed once with water and once with brine
  4. dry with materialsequentially, and then the ethyl acetate layer was dried over anhydrous sodium sulfate
  5. filtrationThe insoluble was filtered off
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customthe resulting residue was purified by silica gel column chromatography (silica gel cartridge, hexane:ethyl acetate=100:0-50:50)

Sources & evidence

ORD record
ord-28d0c613d4444b85b5d37677c39d04df
Source dataset
uspto-grants-2016_08
Patent number
US09428483B2

Reaction notes

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