Hydrochloric Acid → benzhydryl (6R,7R)-7-[[(2Z)-2-(2-benzhydryloxy-2-oxoethoxy)imino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-3-[2,2,2-triphenyl-1-(1H-triazol-4-ylsulfanyl)ethyl]sulfanyl-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 1707461Notes

Reaction equation

HRID 1707461 reaction equation
[C:1]1([CH:7]([O:14][C:15]([C:17]2[N:22]3[C:23](=[O:26])[C@@H:24]([NH2:25])[C@H:21]3[S:20][CH2:19][C:18]=2[S:27][CH:28]([C:35]([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[S:29][C:30]2[N:31]=[N:32][NH:33][CH:34]=2)=[O:16])[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:54]([NH:73][C:74]1[S:75][CH:76]=[C:77](/[C:79](=[N:83]/[O:84][CH2:85][C:86]([O:88][CH:89]([C:96]2[CH:101]=[CH:100][CH:99]=[CH:98][CH:97]=2)[C:90]2[CH:95]=[CH:94][CH:93]=[CH:92][CH:91]=2)=[O:87])/[C:80](O)=[O:81])[N:78]=1)([C:67]1[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=1)([C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1)[C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1.CN1CCOCC1.P(Cl)(Cl)(OC1C=CC=CC=1)=O.Cl>ClC.O>[C:1]1([CH:7]([O:14][C:15]([C:17]2[N:22]3[C:23](=[O:26])[C@@H:24]([NH:25][C:80](=[O:81])/[C:79](/[C:77]4[N:78]=[C:74]([NH:73][C:54]([C:55]5[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=5)([C:61]5[CH:62]=[CH:63][CH:64]=[CH:65][CH:66]=5)[C:67]5[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=5)[S:75][CH:76]=4)=[N:83]\[O:84][CH2:85][C:86]([O:88][CH:89]([C:96]4[CH:101]=[CH:100][CH:99]=[CH:98][CH:97]=4)[C:90]4[CH:91]=[CH:92][CH:93]=[CH:94][CH:95]=4)=[O:87])[C@H:21]3[S:20][CH2:19][C:18]=2[S:27][CH:28]([C:35]([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)([C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=2)[C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)[S:29][C:30]2[N:31]=[N:32][NH:33][CH:34]=2)=[O:16])[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 13038Phosphorodichloridic acid, phenyl esterHCID 13938984(2Z)-2-(2-benzhydryloxy-2-oxoethoxy)imino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetic acidHCID 178511753HCID 178511753, compound

Product 1

HCID 88301232benzhydryl (6R,7R)-7-[[(2Z)-2-(2-benzhydryloxy-2-oxoethoxy)imino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-3-[2,2,2-triphenyl-1-(1H-triazol-4-ylsulfanyl)ethyl]sulfanyl-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateYield 73%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6327Methyl ChlorideSolvent

Conditions

Temperature
-30 °C

Procedure

To a solution of 7β-amino-3-(trityl-1,2,3-triazol-4-ylthiomethyl-thio)-3-cephem-4-carboxylic acid diphenylmethyl ester (800 mg: 1.06 mMol.) and (Z)-2-(2-tritylaminothiazol-4-yl)-2-(diphenylmethoxycarbonylmethoxyimino)acetic acid (728 mg: 1.11 mMol.) in chloromethane (8 ml) cooling at -30° C. are added N-methylmorpholine (0.27 ml: 2.46 mMol.), phenyl dichlorophosphate (0.19 ml: 1.27 mMol.), and the mixture is stirred at -30° C. for 30 minutes. The reaction mixture is mixed with 10% hydrochloric acid (1 ml), diluted with water, and extracted with ethyl acetate. The extract washed with brine, dried over sodium sulfate, and concentrated. The residue is purified by silica gel chromatography (toluene: ethyl acetate=10:1) to give 7β-[(Z)-2-(2-tritylaminothiazol-4-yl)-2-(diphenylmethoxycarbonylmethoxyimino)acetamido]-3-(trityl-1,2,3-triazol-4-ylthiomethylthio)-3-cephem-4-carboxylic acid diphenylmethyl ester (1.07 g) as yellow foam. Yield: 73%.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe extract washed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue is purified by silica gel chromatography (toluene: ethyl acetate=10:1)

Sources & evidence

ORD record
ord-c95db29e49bb467bb54b042b4f93de16
Source dataset
uspto-grants-1994_10
Patent number
US05352792

Reaction notes

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