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 743052ノート

反応式

HRID 743052 の反応式
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]

参加物

6

反応物 4

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 128330237-Amino-3-methoxymethyl-3-cephem-4-carboxylic acidHCID 133930641-Iodoethyl 2,2-dimethylpropanoateHCID 14459662(2Z)-2-[2-(tritylamino)-1,3-thiazol-4-yl]-2-trityloxyiminoacetyl chloride

生成物 1

HCID 144597281-(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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

反応条件

温度
0 °C

実験手順

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).

後処理

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

出典と根拠

ORDレコード
ord-5f5c944cd2024b388c72b042ba29b1f3
出典データセット
uspto-grants-1996_09
特許番号
US05556850

反応ノート

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