Reaktion #463757

Reaktionsgleichung

n-Butyl lithium

diphenylmethyl 7-phenylacetamido-3-triflyloxyceph-3-em-4-carboxylate

(tetrahydrofuran-2-yl)tri-n-butylstannane

triflate

→

title compound

Diphenylmethyl (6R,7R)-7-phenylacetamido-3-(tetrahydrofuran-2-yl)ceph-2-em-4-carboxylate

Lösungsmittel

THF

hexane

N-methylpyrrolidinone

THF

dimethyl sulphide

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwas then added
2. 2
   Temperaturwas then cooled to -78° C
3. 3
   workup.STIRRINGThe red-brown homogeneous solution was stirred for 30 min. at -78° C
4. 4
   Temperaturwas then cooled to -78° C
5. 5
   Sonstigethen quenched by the addition of saturated aq. ammonium chloride (30ml)
6. 6
   Temperaturto warm to room temperature
7. 7
   workup.ADDITIONthen diluted with water (100ml)
8. 8
   Extraktionextracted with ethyl acetate (100ml, 30ml)
9. 9
   WaschenThe combined organic phases were washed with water, brine
10. 10
    Trocknendried over magnesium sulphate
11. 11
    SonstigeAfter removal of the solvents under reduced pressure the crude
12. 12
    Sonstigereaction product
13. 13
    Sonstigewas purified by flash chromatography on silica gel using 10-30% ethyl acetate/methylene dichloride as eluent
14. 14
    WaschenAfter elution of the 3-n-butylcephem

Vorschrift

A solution of (tetrahydrofuran-2-yl)tri-n-butylstannane (J. S. Sawyer, A. Kucerovy, T. L. MacDonald, and G. J. McGarvey, J. Amer. Chem. Soc., 1988, 110, 842) (3.0g, 8.30 mmol) in THF (20ml) was cooled to -78° C. n-Butyl lithium (6.23ml of a 1.6M solution in hexane, 9.97mmol) was then added and the solution was stirred for 15 min. at -78° C. A second flask containing copper (I) bromide.dimethyl sulphide complex (0.854g, 4.14mmol) suspended in a mixture of dimethyl sulphide (15ml) and THF (30ml) was then cooled to -78° C. The α-lithiotetrahydrofuran species was transferred via a cannula to the suspension of copper bromide at -78° C. The red-brown homogeneous solution was stirred for 30 min. at -78° C. A third flask containing a solution of diphenylmethyl 7-phenylacetamido-3-triflyloxyceph-3-em-4-carboxylate (V. Farina, S. R. Baker, and S. I. Hanck, J. Org. Chem., 1989, 54, 4962) (1.9g, 3.0mmol) in a mixture of N-methylpyrrolidinone (20ml) and THF (50ml) was then cooled to -78° C. The cuprate species was transferred via a cannula to the solution of triflate at -78° C. The reaction mixture was stirred for 1h at -78° C. then quenched by the addition of saturated aq. ammonium chloride (30ml). The resulting mixture was allowed to warm to room temperature then diluted with water (100ml) and extracted with ethyl acetate (100ml, 30ml). The combined organic phases were washed with water, brine, then dried over magnesium sulphate. After removal of the solvents under reduced pressure the crude reaction product was purified by flash chromatography on silica gel using 10-30% ethyl acetate/methylene dichloride as eluent. After elution of the 3-n-butylcephem, the title compound was obtained as a mixture of diastereoisomers of the Δ2 and Δ3 cephems (1.014g, 61%).

Quelle