Hydrochloric Acid → 7-[2-(2-aminothiazol-4-yl)-2-(2-hydroxyethoxyimino)acetamido]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid hydrochloride

HRID 255766Notes

Reaction equation

HRID 255766 reaction equation
C([NH:3][C:4]1[S:5][CH:6]=[C:7]([C:9](=[N:33][O:34][CH2:35][CH2:36][O:37]C=O)[C:10]([NH:12][CH:13]2[C:31](=[O:32])[N:15]3[C:16]([C:28]([OH:30])=[O:29])=[C:17]([CH2:20][S:21][C:22]4[N:26]([CH3:27])[N:25]=[N:24][N:23]=4)[CH2:18][S:19][C@H:14]23)=[O:11])[N:8]=1)=O.[ClH:40].O1CCCC1>CO>[ClH:40].[NH2:3][C:4]1[S:5][CH:6]=[C:7]([C:9](=[N:33][O:34][CH2:35][CH2:36][OH:37])[C:10]([NH:12][CH:13]2[C:31](=[O:32])[N:15]3[C:16]([C:28]([OH:30])=[O:29])=[C:17]([CH2:20][S:21][C:22]4[N:26]([CH3:27])[N:25]=[N:24][N:23]=4)[CH2:18][S:19][C@H:14]23)=[O:11])[N:8]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 1317152927-[2-(2-formamidothiazol-4-yl)-2-(2-formyloxyethoxyimino)acetamido]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid

Product 1

HCID 1317152937-[2-(2-aminothiazol-4-yl)-2-(2-hydroxyethoxyimino)acetamido]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid hydrochlorideYield 103.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 7-[2-(2-formamidothiazol-4-yl)-2-(2-formyloxyethoxyimino)acetamido]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer, 2.3 g.), conc. hydrochloric acid (1.6 g.), tetrahydrofuran (17.0 ml.) and methanol (17.0 ml.) was stirred at room temperature for 7.6 hours. After concentrating the resultant solution in vacuo, the residue was pulverized with a mixture of methanol and diisopropyl ether. The precipitates were collected by filtration, washed with diisopropyl ether and dried to give 7-[2-(2-aminothiazol-4-yl)-2-(2-hydroxyethoxyimino)acetamido]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid hydrochloride (syn isomer, 2.3 g.). Water (40 ml.) was added to the product and adjusted to pH 7.0 with sodium bicarbonate. After adjusting the solution to pH 4.0 with 1N hydrochloric acid, the solution was subjected to column chromatography on nonionic adsorption resin "Diaion HP-20" (Trademark, manufactured by Mitsubishi Chemical Industries Ltd.). The column was washed with water and eluted with 20% isopropyl alcohol. The eluate was concentrafted in vacuo and lyophilized to give 7-[2-(2-aminothiazol-4-yl)-2-(2-hydroxyethoxyimino)acetamido]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer, 1.50 g.).

Workup

  1. concentrationAfter concentrating the resultant solution in vacuo
  2. additionthe residue was pulverized with a mixture of methanol and diisopropyl ether
  3. filtrationThe precipitates were collected by filtration
  4. washwashed with diisopropyl ether
  5. customdried

Sources & evidence

ORD record
ord-455ab4aeea394682a72daf998ae6a2ae
Source dataset
uspto-grants-1987_10
Patent number
US04698337

Reaction notes

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