Hydrochloric Acid → Cefotiam

HRID 1111439Notes

Reaction equation

HRID 1111439 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[C:5]([CH2:7][C:8]([NH:10][C@@H:11]2[C:23](=[O:24])[N:13]3[C:14]([C:20]([O-:22])=[O:21])=[C:15]([CH2:18]O)[CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1.[Na+].Cl.[CH3:27][N:28]([CH3:37])[CH2:29][CH2:30][N:31]1[C:35]([SH:36])=[N:34][N:33]=[N:32]1.P(OC)(OC)OC.Cl>C(N)=O.O.CCOCC>[NH2:1][C:2]1[S:3][CH:4]=[C:5]([CH2:7][C:8]([NH:10][C@@H:11]2[C:23](=[O:24])[N:13]3[C:14]([C:20]([OH:22])=[O:21])=[C:15]([CH2:18][S:36][C:35]4[N:31]([CH2:30][CH2:29][N:28]([CH3:37])[CH3:27])[N:32]=[N:33][N:34]=4)[CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 8472Trimethyl phosphiteHCID 23719983HCID 23719983, compoundHCID 178483733HCID 178483733, compound

Product 1

HCID 43708Cefotiam

Reagents, catalysts & solvents 3

HCID 713FormamideSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Procedure

In a mixture of 4 ml of formamide and 4 ml of acetonitrole was suspended 423 mg of sodium 7β-[2-(2-aminothiazol-4-yl)acetamido]-3-hydroxymethyl-3-cephem-4-carboxylate.dihydrate. To the suspension were added in sequence 315 mg of 1-(2-dimethylaminoethyl)-5-mercapto-1H-tetrazole hydrochloride, 0.45 ml of trimethyl phosphite and 0.20 ml of ether solution of hydrogen chloride (5 mol./l). The mixture was stirred at 20~25° C. for 1.5 hour, and there was added 5 ml of water, followed by concentration under reduced pressure at 20 to 25° C. To the concentrated solution was added 50 ml of water, whose pH was adjusted to 5.8 with 1N NaOH, followed by subjecting the resultant to an Amberlite XAD-2 column chromatography, eluting with a mixture of water and acetone (4:1,v/v). Fractions containing the end product were combined, concentrated under reduced pressure and then freeze-dried to give 7β-[ 2-(2-aminothiazol-4-yl) acetamido]-3-[1-(2-dimethylaminoethyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid.

Workup

  1. concentrationfollowed by concentration under reduced pressure at 20 to 25° C
  2. additionTo the concentrated solution was added 50 ml of water, whose pH
  3. washeluting with a mixture of water and acetone (4:1,v/v)
  4. additionFractions containing the end product
  5. concentrationconcentrated under reduced pressure
  6. customfreeze-dried

Sources & evidence

ORD record
ord-9c4ea7692b0543d698e833b23aca193b
Source dataset
uspto-grants-1990_12
Patent number
US04980464

Reaction notes

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