Dicyclohexylcarbodiimide → benzhydryl (6R,7R)-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-7-[[(2Z)-2-(2-oxopyrrolidin-3-yl)oxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 745349Notes

Reaction equation

HRID 745349 reaction equation
[C:1]([NH:20][C:21]1[S:22][CH:23]=[C:24](/[C:26](=[N:30]/[O:31][CH:32]2[CH2:36][CH2:35][NH:34][C:33]2=[O:37])/[C:27](O)=[O:28])[N:25]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:38][C@@H:39]1[C:70](=[O:71])[N:41]2[C:42]([C:54]([O:56][CH:57]([C:64]3[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=3)[C:58]3[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=3)=[O:55])=[C:43]([CH2:46][S:47][C:48]3[N:52]([CH3:53])[N:51]=[N:50][N:49]=3)[CH2:44][S:45][C@H:40]12.ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1>O1CCCC1>[C:1]([NH:20][C:21]1[S:22][CH:23]=[C:24](/[C:26](=[N:30]/[O:31][CH:32]2[CH2:36][CH2:35][NH:34][C:33]2=[O:37])/[C:27]([NH:38][C@@H:39]2[C:70](=[O:71])[N:41]3[C:42]([C:54]([O:56][CH:57]([C:64]4[CH:65]=[CH:66][CH:67]=[CH:68][CH:69]=4)[C:58]4[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=4)=[O:55])=[C:43]([CH2:46][S:47][C:48]4[N:52]([CH3:53])[N:51]=[N:50][N:49]=4)[CH2:44][S:45][C@H:40]23)=[O:28])[N:25]=1)([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 12873516(6R,7R)-Benzhydryl 7-amino-3-((1-methyl-1H-tetrazol-5-ylthio)methyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateHCID 13335553(2Z)-2-(2-oxopyrrolidin-3-yl)oxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetic acid

Product 1

HCID 141554879benzhydryl (6R,7R)-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-7-[[(2Z)-2-(2-oxopyrrolidin-3-yl)oxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateYield 59%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3.25 g of (Z)-2-(2-tritylaminothiazol-4-yl)-2-[(2-pyrrolidon-3-yl)oxyimino]acetic acid are dissolved in 200 ml of tetrahydrofuran, and 3.14 g of benzhydryl 7β-amino-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-3-cephem-4-carboxylate, 1.03 g of 1-hydroxybenzotriazole and 1.57 g of dicyclohexylcarbodiimide are added thereto. The mixture is stirred at room temperature for 2 hours. Insoluble materials are filtered off, and the filtrate is concentrated to dryness under reduced pressure. The residue is dissolved in ethyl acetate, and washed with 1% hydrochloric acid, 5% aqueous sodium bicarbonate solution and an aqueous saturated sodium chloride solution, successively. The ethyl acetate solution is then dried and concentrated to dryness under reduced pressure. The residue thus obtained is purified by silica gel chromatography (solvent, ethyl acetate: benzene=5:2). 3.7 g of benzhydryl 7β-{(Z)-2-(2-tritylaminothiazol-4-yl)-2-[(2-pyrrolidon-3-yl)oxyimino]acetamido}-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl] -3-cephem-4-carboxylate are obtained.

Workup

  1. filtrationInsoluble materials are filtered off
  2. concentrationthe filtrate is concentrated to dryness under reduced pressure
  3. dissolutionThe residue is dissolved in ethyl acetate
  4. washwashed with 1% hydrochloric acid, 5% aqueous sodium bicarbonate solution
  5. dry with materialThe ethyl acetate solution is then dried
  6. concentrationconcentrated to dryness under reduced pressure
  7. customThe residue thus obtained
  8. customis purified by silica gel chromatography (solvent, ethyl acetate: benzene=5:2)

Sources & evidence

ORD record
ord-6ce8be73a0f74ddf840bbc2f3d3f1446
Source dataset
uspto-grants-1986_07
Patent number
US04598075

Reaction notes

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