| 摘要 |
1529448 1<SP>1</SP>-Ethoxycarbonyloxy-ethyl 6-(hexahydro-1H-azepin-1-yl-methyleneamino)-penicillanate LEO PHARMACEUTICAL PRODUCTS Ltd AS 8 Oct 1976 [29 Oct 1975] 44676/75 Heading C2C [Also in Division A5] Novel crystalline diastereomeric forms of 1<SP>1</SP> - ethoxycarbonyloxyethyl - 6 - (hexahydro- 1H - azepin - 1 - yl - methyleneamino) - penicillenate or its hydrochloride are prepared (a) by adding an equivalent of HCl in propanol- 2 to an ethereal solution of mixture of the free base forms, treating the isolated crystals with acetone and recrystallizing them from methanolether to give one diastereomeric hydrochloride, and evaporating the mother liquor and treating the residue with methanol-ether or propanol-2- diisopropyl ether to crystallize the other diastereomeric hydrochloride; or (b) by dissolving the free base in ether, adding cold water, adjusting to pH3À0 with NHCl, freeze-drying the aqueous phase, treating the amorphous mixture with acetone to crystallize one diastereomeric hydrochloride, evaporating the mother liquor, treating the residue with aqueous NaHCO 3 , purifying the liberated base with an ionexchange resin, converting it to the hydrochloride and crystallizing it from ethyl acetate to give the other diastereomeric hydrochloride; or (c) by neutralizing an aqueous solution of the diastereomeric hydrochloride with a base, such as NaHCO 3 to crystallize the diastereomeric base. 1<SP>1</SP>-Ethoxycarbonyloxyethyl 6-(hexahydro-1H- azepin-1-yl-methyleneamino)-penicillinate is prepared as an amorphous mixture of diastereomers by reacting potassium benzylpenicillanate with 1-chloroethylethyl carbonate, treating the resulting 1<SP>1</SP>-ethoxycarbonyloxyethyl benzylpenicillanate with phosphorus pentachloride and quinoline in chloroform, and treating the resulting 1<SP>1</SP>-ethoxycarbonyloxyethyl 6-amino-penicillanate with the dimethyl sulphate complex of N-formyl-hexamethyleneimine. |
