Phosphate → HCID 131718755, compound

HRID 1708520Notes

Reaction equation

HRID 1708520 reaction equation
[CH2:1]([O:4][C:5]([CH2:7][N:8]1[CH2:11][CH2:10][C:9]1=[O:12])=[O:6])[CH:2]=[CH2:3].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].C[Si](C)(C)Cl.P(Cl)(OC1C=CC=CC=1)(O[C:31]1[CH:36]=CC=C[CH:32]=1)=O.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.P([O-])([O-])([O-])=O>O1CCCC1.CN(C)C=O>[CH2:1]([O:4][C:5]([C:7]1[N:8]2[C:9](=[O:12])[CH2:10][C@H:11]2[CH:31]([CH3:36])[CH:32]=1)=[O:6])[CH:2]=[CH2:3]

Participants

9

Reactant 6

HCID 1061PhosphateHCID 6397ChlorotrimethylsilaneHCID 75654Diphenyl chlorophosphateHCID 2724141Tetrabutylammonium FluorideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 17992863HCID 17992863, compound

Product 1

HCID 131718755HCID 131718755, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-50 °C

Procedure

A solution of (3S,4S)-3-[(1R)-1-t-butyldimethylsilyloxyethyl]-4-{(1R)-1-]((4R)-pyrrolidine-2-thion-4-ylthio)carbonyl]-ethyl}-1-(allyloxycarbonylmethyl)-2-azetidinone (1.028 g) in tetrahydrofuran (6 ml) is added dropwise to 1M solution (6.6 ml) of sodium bis(trimethylsilyl)amide in tetrahydrofuran at -60° C. to -50° C. over a period of 5 minutes. The mixture is stirred at -50° C. for 10 minutes, and thereto is added trimethylchlorosilane (0.58 ml) at -60° C. The mixture is stirred at the same temperature for 15 minutes, and thereto is added diphenyl chlorophosphate (0.44 ml) at -60° C. The mixture is stirred at 0° C. for 1.5 hour, and to the reaction mixture is added dimethylformamide (10 ml) at 0° C., and further thereto is added dropwise 1M solution (1.6 ml) of tetra-n-butylammonium fluoride in tetrahydrofuran at -60° C. The mixture is stirred at -50° C. for 30 minutes, and warmed to -20° C. over a period of one hour. After the reaction is complete, the reaction solution is poured into a phosphate buffer (pH 7.0, 20 ml), and the mixture is extracted with ethyl acetate. The aqueous layer is extracted with ethyl acetate, and the ethyl acetate layers are combined, washed twice with water, dried over magnesium sulfate, and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (solvent; n-hexane:chloroform:ethyl acetate=5:5:4) to give (1R,5S,6S)-2-[(4R)-pyrrolidine-2-thion-4-ylthio]-6-](1R)-1-t-butyldimethylsilyloxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid allyl ester (575 mg).

Workup

  1. stirringThe mixture is stirred at the same temperature for 15 minutes
  2. stirringThe mixture is stirred at 0° C. for 1.5 hour
  3. stirringThe mixture is stirred at -50° C. for 30 minutes
  4. temperaturewarmed to -20° C. over a period of one hour
  5. extractionthe mixture is extracted with ethyl acetate
  6. extractionThe aqueous layer is extracted with ethyl acetate
  7. washwashed twice with water
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue is purified by silica gel column chromatography (solvent; n-hexane:chloroform:ethyl acetate=5:5:4)

Sources & evidence

ORD record
ord-d838e69783374de3b7a26e3070ace10a
Source dataset
uspto-grants-1994_10
Patent number
US05359059

Reaction notes

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