Sodium Carbonate → Cefmenoxime sodium

HRID 231342Notes

Reaction equation

HRID 231342 reaction equation
[NH2:1][C@@H:2]1[C:20](=[O:21])[N:4]2[C:5]([C:17]([OH:19])=[O:18])=[C:6]([CH2:9][S:10][C:11]3[N:15]([CH3:16])[N:14]=[N:13][N:12]=3)[CH2:7][S:8][C@H:3]12.C(=O)([O-])O.[Na+:26].Br[CH2:28][C:29](=O)[C:30](=[N:34][O:35][CH3:36])[C:31](Cl)=[O:32].[NH2:38][C:39]([NH2:41])=[S:40].C(=O)([O-])[O-].[Na+].[Na+]>O1CCCC1.O>[NH2:41][C:39]1[S:40][CH:28]=[C:29](/[C:30](=[N:34]/[O:35][CH3:36])/[C:31]([NH:1][C@@H:2]2[C:20](=[O:21])[N:4]3[C:5]([C:17]([O-:19])=[O:18])=[C:6]([CH2:9][S:10][C:11]4[N:15]([CH3:16])[N:14]=[N:13][N:12]=4)[CH2:7][S:8][C@H:3]23)=[O:32])[N:38]=1.[Na+:26]

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 483175(6R,7R)-7-Amino-3-(((1-methyl-1H-tetrazol-5-yl)thio)methyl)-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acidHCID 516892Sodium BicarbonateHCID 2723790ThioureaHCID 534266374-Bromo-2-(methoxyimino)-3-oxobutanoyl chloride

Product 1

HCID 23676080Cefmenoxime sodiumYield 88.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent2×

Procedure

In a solvent mixture of 50 ml water and 35 ml tetrahydrofuran were dissolved 1.64 g of 7β-amino-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid and 1.68 g of sodium hydrogen carbonate. To this solution was added a solution of 2.1 g 4-bromo-2-methoxyimino-3-oxobutyryl chloride in 15 ml tetrahydrofuran and the mixture was stirred at 20°-25° C. for 5 minutes. Then, a solution of 1.52 g thiourea in 20 ml water was added thereto and the mixture was stirred at the same temperature for 1 hour. The reaction mixture was adjusted to pH 7.0 with 20% aqueous sodium carbonate solution and concentrated under reduced pressure. The concentrate was subjected to column chromatography using Diaion HP-40 (Mitsubishi Chemical Industries, Ltd.) and elution was carried out with 400 ml of water-isopropyl alcohol (9:1, v/v). The eluate was lyophilized to give 2.35 g of sodium 7β-[2-(2-aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamido]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylate. Yield 88.2%. Analysis by high-performance liquid chromatography showed that the proportion of the (E)-isomer was not more than 1% of the (Z)-isomer.

Workup

  1. stirringthe mixture was stirred at the same temperature for 1 hour
  2. concentrationconcentrated under reduced pressure
  3. washDiaion HP-40 (Mitsubishi Chemical Industries, Ltd.) and elution

Sources & evidence

ORD record
ord-be882b54e4974b72bbba61b26b31f860
Source dataset
uspto-grants-1989_07
Patent number
US04845257

Reaction notes

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