Hydrochloric Acid → benzhydryl (6R,7R)-7-[[(2Z)-2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-trityloxyiminoacetyl]amino]-8-oxo-3-(pyridin-2-ylsulfanylmethylsulfanyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 1707447Notes

Reaction equation

HRID 1707447 reaction equation
C([S:4][CH2:5][S:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=1)(=O)C.C[O-].[Na+].CO.[C:18]1([CH:24]([O:31][C:32]([C:34]2[N:39]3[C:40](=[O:80])[C@@H:41]([NH:42][C:43](=[O:79])/[C:44](/[C:66]4[N:67]=[C:68]([NH:71][C:72]([O:74][C:75]([CH3:78])([CH3:77])[CH3:76])=[O:73])[S:69][CH:70]=4)=[N:45]\[O:46][C:47](C4C=CC=CC=4)([C:54]4[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=4)[C:48]4[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=4)[C@H:38]3[S:37][CH2:36][C:35]=2OS(C)(=O)=O)=[O:33])C2C=CC=CC=2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.Cl>CN(C)C=O.O1CCCC1.O>[C:18]1([CH:24]([O:31][C:32]([C:34]2[N:39]3[C:40](=[O:80])[C@@H:41]([NH:42][C:43](=[O:79])/[C:44](/[C:66]4[N:67]=[C:68]([NH:71][C:72]([O:74][C:75]([CH3:77])([CH3:76])[CH3:78])=[O:73])[S:69][CH:70]=4)=[N:45]\[O:46][C:47]([C:48]4[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=4)([C:48]4[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=4)[C:54]4[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=4)[C@H:38]3[S:37][CH2:36][C:35]=2[S:4][CH2:5][S:6][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=2)=[O:33])[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 10260338benzhydryl (6R,7R)-7-[[(2Z)-2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-trityloxyiminoacetyl]amino]-3-methylsulfonyloxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateHCID 104653712-AcetylthiomethylthiopyridineHCID 23694274Sodium methanolate methanol

Product 1

HCID 16143732benzhydryl (6R,7R)-7-[[(2Z)-2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-trityloxyiminoacetyl]amino]-8-oxo-3-(pyridin-2-ylsulfanylmethylsulfanyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateYield 145.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 2-acetylthiomethylthiopyridine (249 mg: 1.25 mMol.) in a mixture of dimethylformamide (4 ml) and tetrahydrofuran (2 ml) cooling at -78° C. is added dropwise 1.26N-sodium methoxide-methanol solution (0.87 ml: 1.10 mMol.), and the mixture is stirred at -78° C. for 15 minutes. To this reaction mixture is added a solution of 7β-[(Z)-2-(2-t-butoxycarbonylaminothiazol-4-yl)-2-trityloxyiminoacetamido]-3-methanesulfonyloxy-3-cephem-4-carboxylic acid diphenylmethyl ester (971 mg: 1.00 mMol.) in dimethylformamide (2 ml) and the mixture is stirred at -78° C. for 1 hour. The reaction mixture is mixed with 10% hydrochloric acid to stop the reaction, diluted with water, and extracted with ethyl acetate. The extract is washed with dilute aqueous sodium hydrogen carbonate and brine, dried over sodium sulfate, and concentrated. The residue is purified by silica gel chromatography (toluene: ethyl acetate=4:1) and silica gel rechromatography (toluene: ethyl acetate=7:1) to give 7β-[(Z)-2-(2-t-butoxycarbonylaminothiazol-4-yl)-2-trityloxyiminoacetamido]-3-(pyrid-2-ylthiomethylthio)-3-cephem-4-carboxylic acid diphenylmethyl ester as colorless foam (753 mg). Yield: 73%.

Workup

  1. stirringthe mixture is stirred at -78° C. for 1 hour
  2. customthe reaction
  3. extractionextracted with ethyl acetate
  4. washThe extract is washed with dilute aqueous sodium hydrogen carbonate and brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customThe residue is purified by silica gel chromatography (toluene: ethyl acetate=4:1) and silica gel rechromatography (toluene: ethyl acetate=7:1)

Sources & evidence

ORD record
ord-28e6e66af4784d16969c27dd8bbd08da
Source dataset
uspto-grants-1994_10
Patent number
US05352792

Reaction notes

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