1,8-Diazabicyclo(5.4.0)undec-7-ene → 1-(2,2-dimethylpropanoyloxy)ethyl (6R)-3-(methoxymethyl)-8-oxo-7-[[(2Z)-2-[2-(tritylamino)-1,3-thiazol-4-yl]-2-trityloxyiminoacetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 743052Notes

Reaction equation

C1CCN2C(=NCCC2)CC1.[NH2:12][CH:13]1[C:26](=[O:27])[N:15]2[C:16]([C:23]([OH:25])=[O:24])=[C:17]([CH2:20][O:21][CH3:22])[CH2:18][S:19][C@H:14]12.[CH3:28][C:29]([CH3:37])([CH3:36])[C:30]([O:32][CH:33](I)[CH3:34])=[O:31].[C:38]([NH:57][C:58]1[S:59][CH:60]=[C:61](/[C:63](=[N:67]/[O:68][C:69]([C:82]2[CH:87]=[CH:86][CH:85]=[CH:84][CH:83]=2)([C:76]2[CH:81]=[CH:80][CH:79]=[CH:78][CH:77]=2)[C:70]2[CH:75]=[CH:74][CH:73]=[CH:72][CH:71]=2)/[C:64](Cl)=[O:65])[N:62]=1)([C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)([C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1>C(Cl)Cl>[CH3:22][O:21][CH2:20][C:17]1[CH2:18][S:19][C@@H:14]2[CH:13]([NH:12][C:64](=[O:65])/[C:63](/[C:61]3[N:62]=[C:58]([NH:57][C:38]([C:51]4[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=4)([C:45]4[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=4)[C:39]4[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=4)[S:59][CH:60]=3)=[N:67]\[O:68][C:69]([C:82]3[CH:87]=[CH:86][CH:85]=[CH:84][CH:83]=3)([C:76]3[CH:77]=[CH:78][CH:79]=[CH:80][CH:81]=3)[C:70]3[CH:71]=[CH:72][CH:73]=[CH:74][CH:75]=3)[C:26](=[O:27])[N:15]2[C:16]=1[C:23]([O:25][CH:33]([O:32][C:30](=[O:31])[C:29]([CH3:37])([CH3:36])[CH3:28])[CH3:34])=[O:24]

Participants

Conditions

Temperature: 0 °C

Procedure

9.5 ml (64 mmol) of DBU are slowly added to a suspension of 14.0 g (57 mmol) of 7-amino-3-methoxymethyl-3-cephem-4-carboxylic acid in 160 ml of anhydrous methylene chloride at 0° C. and the mixture is subsequently stirred at 0° C. for 30 minutes. 20.8 g (81 mmol) of 1-iodoethyl 2,2-dimethylpropionate are then added and the mixture is stirred at 0° C. for a further 30 minutes and then allowed to warm to room temperature in the course of 30 minutes. After renewed cooling to 0° C., the crude 2-(2-tritylaminothiazol-4-yl)-2-(Z)-trityloxyiminoacetyl chloride (≃ 54 mmol), dissolved in 100 ml of methylene chloride, is added dropwise and the mixture is then stirred at 0° C. for a further 2 hours. The reaction mixture is concentrated in vacuo and the residue is taken up in ethyl acetate. The mixture is washed successively with 5% sodium thiosulfate solution, saturated sodium bicarbonate solution and saturated sodium chloride solution, and the organic phase is dried over sodium sulfate and concentrated to dryness in vacuo. The crude product is purified by chromatography on silica gel (35-70 μm) (column: 50 cm×8.5 cm, toluene/ethyl acetate=5/1).

Workup

stirringthe mixture is stirred at 0° C. for a further 30 minutes
temperatureto warm to room temperature in the course of 30 minutes
temperatureAfter renewed cooling to 0° C.
additionis added dropwise
stirringthe mixture is then stirred at 0° C. for a further 2 hours
concentrationThe reaction mixture is concentrated in vacuo
washThe mixture is washed successively with 5% sodium thiosulfate solution, saturated sodium bicarbonate solution and saturated sodium chloride solution
dry with materialthe organic phase is dried over sodium sulfate
concentrationconcentrated to dryness in vacuo
customThe crude product is purified by chromatography on silica gel (35-70 μm) (column: 50 cm×8.5 cm, toluene/ethyl acetate=5/1)

Sources & evidence

ORD record: ord-5f5c944cd2024b388c72b042ba29b1f3
Source dataset: uspto-grants-1996_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05556850

Reaction notes

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