G. J. Kemperman, J. Zhu, A. J. H. Klunder, B. Zwanenburg
FULL PAPER
The complex (2 g) was suspended in ethyl acetate (10 mL). While
stirring the suspension 5% HCl (ഠ2 mL) was added until both
layers had turned completely clear. The aqueous layer was separ-
ated and washed with ethyl acetate (5 mL). The thus-obtained
aqueous Cephalexin solution was cooled below 5 °C. The pH was
raised to 3 with 25% ammonia and then to a pH of 4 with 5%
ammonia, resulting in precipitation of the Cephalexin. The mixture
was maintained at a temperature below 5 °C for another 30 min.,
after which the product was collected by filtration. After drying
under a flow of nitrogen 1.45 g of Cephalexin monohydrate (94%
for the decomplexation, 68% overall for 7-ADCA) was obtained as
a white solid. The product had a purity of 97% according to HPLC.
X-ray powder diffraction confirmed that the desired Cephalexin
monohydrate had indeed been obtained.
Acknowledgments
This project was financially supported by DSM Life Sciences
Group (Geleen, The Netherlands) and by the Dutch ministry of
economical affairs (Senter). Dr. Ben de Lange (DSM Research, Ge-
leen, The Netherlands) is kindly acknowledged for valuable discus-
sions.
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described for Cephalexin except that the sodium Dane salt of ra-
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ylglycine Dane Salt: This procedure was essentially the same as that
described for Cephalexin except that the potassium Dane salt of
racemic p-hydroxyphenylglycine (3.17 g, 10.0 mmol) was used as a
suspension in dichloromethane (15 mL) and dimethylformamide (2
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yield of 60% (2.70 g). After decomplexation, which was carried out
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Patent has been filed by DSM Life Sciences Group, The
Netherlands, NL1013402, 1999; PCT/NL00/0063, 2000.
Received November 27, 2000
[O00596]
1820
Eur. J. Org. Chem. 2001, 1817Ϫ1820