Reaktion #1508982

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

N-methylpyrrolidinone

THF

THF

hexane

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 -18° C
5. 5
   workup.STIRRINGThe reaction mixture was stirred for 1 h at -78° C.
6. 6
   Sonstigethen quenched by the addition of saturated aq. ammonium chloride (30 ml)
7. 7
   Temperaturto warm to room temperature
8. 8
   workup.ADDITIONthen diluted with water (100 ml)
9. 9
   Extraktionextracted with ethyl acetate (100 ml, 30 ml)
10. 10
    WaschenThe combined organic phases were washed with water, brine
11. 11
    Trocknendried over magnesium sulphate
12. 12
    SonstigeAfter removal of the solvents under reduced pressure the crude
13. 13
    Sonstigereaction product
14. 14
    Sonstigewas purified by flash chromatography on silica gel using 10-30% ethyl acetate/methylene dichloride as eluent
15. 15
    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) (3.0 g, 8.30 mmol) in THF (20 ml) was cooled to -78° C. n-Butyl lithium (6.23 ml of a 1.6M solution in hexane, 9.97 mmol) was then added and the solution was stirred for 15 min. at -78° C. A second flask containing copper (I) bromide.dimethylsulphide complex (0.854 g, 4.14 mmol) suspended in a mixture of dimethyl sulphide (15 ml) and THF (30 ml) 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) (1.9 g, 3.0 mmol) in a mixture of N-methylpyrrolidinone (20 ml) and THF (50 ml) was then cooled to -18° C. The cuprate species was transferred via a cannula to the solution of triflate at -78° C. The reaction mixture was stirred for 1 h at -78° C. then quenched by the addition of saturated aq. ammonium chloride (30 ml). The resulting mixture was allowed to warm to room temperature then diluted with water (100 ml) and extracted with ethyl acetate (100 ml, 30 ml). 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 (1.014 g, 61%).

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