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

HRID 1707438Notes

Reaction equation

HRID 1707438 reaction equation
Cl.[C:2]1([CH:8]([O:15][C:16]([C:18]2[N:23]3[C:24](=[O:27])[C@@H:25]([NH2:26])[C@H:22]3[S:21][CH2:20][C:19]=2[O:28][S:29]([CH3:32])(=[O:31])=[O:30])=[O:17])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:33]([O:37][C:38]([NH:40][C:41]1[S:42][CH:43]=[C:44](/[C:46](=[N:50]/[O:51][CH:52]2[CH2:56][CH2:55][CH2:54][CH2:53]2)/[C:47](O)=[O:48])[N:45]=1)=[O:39])([CH3:36])([CH3:35])[CH3:34].CN1CCOCC1.P(Cl)(Cl)(OC1C=CC=CC=1)=O.Cl>ClCCl.O>[C:2]1([CH:8]([O:15][C:16]([C:18]2[N:23]3[C:24](=[O:27])[C@@H:25]([NH:26][C:47](=[O:48])/[C:46](/[C:44]4[N:45]=[C:41]([NH:40][C:38]([O:37][C:33]([CH3:35])([CH3:34])[CH3:36])=[O:39])[S:42][CH:43]=4)=[N:50]\[O:51][CH:52]4[CH2:56][CH2:55][CH2:54][CH2:53]4)[C@H:22]3[S:21][CH2:20][C:19]=2[O:28][S:29]([CH3:32])(=[O:31])=[O:30])=[O:17])[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 13038Phosphorodichloridic acid, phenyl esterHCID 18963301(2Z)-2-cyclopentyloxyimino-2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]acetic acidHCID 883013187beta-Amino-3-methanesulfonyloxy-3-cephem-4-carboxylic acid diphenylmethyl ester hydrochloride

Product 1

HCID 88300745benzhydryl (6R,7R)-7-[[(2Z)-2-cyclopentyloxyimino-2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]acetyl]amino]-3-methylsulfonyloxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateYield 78%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of 7β-amino-3-methanesulfonyloxy-3-cephem-4-carboxylic acid diphenylmethyl ester hydrochloride (1.49 g: 3 mMol.) and (Z)-2-(2-t-butoxycarbonylaminothiazol-4-yl)-2-cyclopentyloxyimino-acetic acid (1.23 g: 3.5 mMol.) in dichloromethane (30 ml) at -30° C. are added N-methylmorpholine (1.1 ml: 10 mMol.) and, after 1 minute, phenyl dichlorophosphate (0.49 ml: 3.3 mMol.), and the mixture is stirred at the same temperature for 2 hours. The reaction mixture is mixed with 1N-hydrochloric acid (6 ml) and water (50 ml) and extracted with ethyl acetate. The extract is washed with water, 5% aqueous sodium hydrogen carbonate, and water, dried over sodium sulfate, and purified by silica gel chromatography (toluene: ethyl acetate=5:1, containing 0.5% acetic acid) to give 7β-[(Z)-2-(2-t-butoxycarbonylaminothiazol-4-yl)-2-cyclopentyloxyiminoacetamido]-3-methanesulfonyloxy-3-cephem-4-carboxylic acid diphenylmethyl ester (1.86 g) as white foam. Yield: 78%.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe extract is washed with water, 5% aqueous sodium hydrogen carbonate, and water
  3. dry with materialdried over sodium sulfate
  4. custompurified by silica gel chromatography (toluene: ethyl acetate=5:1, containing 0.5% acetic acid)

Sources & evidence

ORD record
ord-b12c8c5620fe4fe5a7a87a809b4c8713
Source dataset
uspto-grants-1994_10
Patent number
US05352792

Reaction notes

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