4-Methylmorpholine → 3-Methoxy-2-cephem-4alpha-carboxylic acid diphenylmethyl ester
Reaction equation
CN1CCOCC1.C(OC(Cl)=O)C(C)C.[C:16]1([CH:22]([O:29][C:30]([C:32]2[N:37]3[C:38](=[O:41])[C@@H:39](N)[C@H:36]3[S:35][CH2:34][C:33]=2[O:42][CH3:43])=[O:31])[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>>[C:16]1([CH:22]([O:29][C:30]([C@@H:32]2[N:37]3[C:38](=[O:41])[CH2:39][C@H:36]3[S:35][CH:34]=[C:33]2[O:42][CH3:43])=[O:31])[C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1Participants
Conditions
- Temperature
- -15 °C
Procedure
If, in the above process, 0.09 g of D-α-tert.-butoxycarbonylamino-α-(1,4-cyclohexadienyl)-acetic acid, 0.038 ml of N-methyl-morpholine and 0.052 ml of chloroformic acid isobutyl ester are used and the mixture is stirred for 30 minutes at -15° C under a nitrogen atmosphere, then treated with 0.125 g of 7β-amino-3-methoxy-3-cephem-4-carboxylic acid diphenylmethyl ester and 0.035 ml of N-methyl-morpholine, stirred for 30 minutes at -10° C and for 30 minutes at 0° C and worked up as described above, a crude product is obtained, which is purified by means of preparative layer chromatography (silica gel; system: diethyl ether; identification with ultraviolet light, λ = 254 μ). At Rf~0.51, 7β- D-α-tert.-butoxycarbonylamino-(1,4-cyclohexadienyl)-acetylamino!-3-methoxy-2-cephem-4α-carboxylic acid diphenylmethyl ester is thus obtained, melting point = 153°-154° C after crystallisation from a mixture of methylene chloride and pentane; thin layer chromatogram (silica gel; identification with iodine): Rf~0.51 (system: diethyl ether); α!D20 = +176° ± 1° (c = 0.541 in chloroform); ultraviolet absorption spectrum (in 95% strength aqueous ethanol): λmax = 257 mμ (ε = 3,600); and infrared absorption spectrum (in methylene chloride): characteristic bands at 2.96 μ, 5.64 μ, 5.76 μ, 5.92 μ, 6.18 μ and 6.75 μ; whilst at Rf~0.39 7β- D-α-tert.-butoxycarbonyl-amino-α-(1,4-cyclohexadienyl)-acetylamino!-3-methoxy-3-cephem-4-carboxylic acid diphenylmethyl ester is obtained, which is identical with the product obtainable according to the process described above.
Workup
- stirringstirred for 30 minutes at -10° C and for 30 minutes at 0° C
- customis obtained
- customwhich is purified by means of preparative layer chromatography (silica gel; system: diethyl ether; identification with ultraviolet light, λ = 254 μ)
Sources & evidence
- ORD record
- ord-1259a242030543a6b642fbbfa1240590
- Source dataset
- uspto-grants-1978_02
- Patent number
- US04073902
Reaction notes
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