Hydrochloric Acid → HCID 178511753, compound

HRID 249597

Reaction equation

HRID 249597 reaction equation
[C:1]1([CH:7]([O:14][C:15]([C:17]2[N:22]3[C:23](=[O:35])[C@@H:24]([NH:25]C(=O)CC4C=CC=CC=4)[C@H:21]3[S:20][CH2:19][C:18]=2[S:36][CH2:37][S:38][C:39]2[N:40]=[N:41][NH:42][CH:43]=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.N1C=CC=CC=1.[C:50](Cl)([C:63]1[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=1)([C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1)[C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1.Cl.P(Cl)(Cl)(Cl)(Cl)Cl.C(O)CC(O)C>ClCCl.O>[C:8]1([CH:7]([O:14][C:15]([C:17]2[N:22]3[C:23](=[O:35])[C@@H:24]([NH2:25])[C@H:21]3[S:20][CH2:19][C:18]=2[S:36][CH:37]([C:50]([C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)([C:63]2[CH:64]=[CH:65][CH:66]=[CH:67][CH:68]=2)[C:57]2[CH:58]=[CH:59][CH:60]=[CH:61][CH:62]=2)[S:38][C:39]2[N:40]=[N:41][NH:42][CH:43]=2)=[O:16])[C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 1049Pyridine2×HCID 6456Trityl chlorideHCID 78961,3-ButanediolHCID 24819Phosphorus pentachlorideHCID 178520256HCID 178520256, compound

Product 1

HCID 178511753HCID 178511753, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent4×

Procedure

To a solution of 7β-phenylacetamido-3-(1,2,3-triazol-4-ylthiomethylthio)-3-cephem-4-carboxylic acid diphenylmethyl ester (10.0 g : 15.9 mMol.) in dichloromethane (100 ml) under ice cooling are added pyridine (1.54 ml : 19.1 mMol.) and trityl chloride (5.32 g 19.1 mMol.), and the mixture is stirred at room temperature for 1 hour. The reaction mixture is mixed with 10% hydrochloric acid (2 ml), diluted with water, and extracted with ethyl acetate. The extract is washed with water, dried over sodium sulfate, and concentrated. To a solution of the residue in dichloromethane (50 ml) under ice cooling are added pyridine (2.57 ml : 31.8 mMol.) and phosphorus pentachloride (5.96 g : 28.6 mMol.), and the mixture is stirred for 30 minutes. The reaction mixture is added dropwise to a solution of 1.3-butanediol (8.6 ml : 95.9 mMol.) in dichloromethane (25 ml) at -30° C. , and the mixture is stirred at -20 to -30° C. for 10 minutes and under ice cooling for 40 minutes. The reaction mixture is mixed with water, diluted with dichloromethane, washed with brine, dried over sodium sulfate, and concentrated. The residue is pulverized with ether, washed with ether, dissolved in dichloromethane, washed with 5% aqueous sodium hydrogen carbonate, dried over sodium sulfate, and concentrated. The residue is purified by silica gel chromatography (toluene : ethyl acetate=2:1) to give 7β-amino-3-(trityl-1,2,3-triazol-4-ylthiomethylthio) -3-cephem-4- carboxylic acid diphenylmethyl ester (6.70 g : pale yellow foam. Yield: 56 %,

Workup

  1. extractionextracted with ethyl acetate
  2. washThe extract is washed with water
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. stirringthe mixture is stirred for 30 minutes
  6. stirringthe mixture is stirred at -20 to -30° C. for 10 minutes and under ice cooling for 40 minutes
  7. washwashed with brine
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated
  10. washwashed with ether
  11. dissolutiondissolved in dichloromethane
  12. washwashed with 5% aqueous sodium hydrogen carbonate
  13. dry with materialdried over sodium sulfate
  14. concentrationconcentrated
  15. customThe residue is purified by silica gel chromatography (toluene : ethyl acetate=2:1)

Sources & evidence

ORD record
ord-ed51c8fd325849e8873d840053a8eec6
Source dataset
uspto-grants-1993_05
Patent number
US05214037

Linked notes

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