Sulfuric Acid → 2-n-Octyloxy-1-n-octyloxymethylethyl 7-[2-(2-formamidothiazol-4-yl)-2-methoxyiminoacetamido]-2-cephem-4-carboxylate

HRID 1632752Notes

Reaction equation

HRID 1632752 reaction equation
[CH:1]([NH:3][C:4]1[S:5][CH:6]=[C:7]([C:9](=[N:25][O:26][CH3:27])[C:10]([NH:12][CH:13]2[C:23](=[O:24])[N:15]3[C:16]([C:20]([OH:22])=[O:21])=[CH:17][CH2:18][S:19][C@H:14]23)=[O:11])[N:8]=1)=[O:2].[CH2:28]([O:36][CH2:37][CH:38]([CH2:40][O:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH3:49])O)[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH3:35].C1(S(Cl)(=O)=O)C=CC=CC=1.S(=O)(=O)(O)O>N1C=CC=CC=1>[CH:1]([NH:3][C:4]1[S:5][CH:6]=[C:7]([C:9](=[N:25][O:26][CH3:27])[C:10]([NH:12][CH:13]2[C:23](=[O:24])[N:15]3[CH:16]([C:20]([O:22][CH:38]([CH2:37][O:36][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH3:35])[CH2:40][O:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH3:49])=[O:21])[CH:17]=[CH:18][S:19][C@H:14]23)=[O:11])[N:8]=1)=[O:2]

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 7369Benzenesulfonyl chlorideHCID 40492571,3-Dioctyl glyceryl etherHCID 1317124427-[2-(2-Formamidothiazol-4-yl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylic acid

Product 1

HCID 1317139162-n-Octyloxy-1-n-octyloxymethylethyl 7-[2-(2-formamidothiazol-4-yl)-2-methoxyiminoacetamido]-2-cephem-4-carboxylateYield 30%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A mixture of 7-[2-(2-formamidothiazol-4-yl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylic acid (syn isomer, 6.0 g) and molecular sieves (20 g) in dry pyridine (60 ml) was stirred at 0° to 5° C. for an hour, and 2-n-octyloxy-1-n-octyloxymethylethanol [4.6 g] was added thereto. Benzenesulfonyl chloride (2.6 g) was dropwise added to the stirred solution at -5° to -3° C. over 30 minutes, and then stirred at 0° C. for an hour. The resultant mixture was poured into the crushed ice (300 g), adjusted to pH 1 to 2 with 20% sulfuric acid, and then extracted with ethyl acetate (300 ml). The extract was washed with a saturated aqueous solution of sodium chloride, an aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride in turn, and dried over anhydrous magnesium sulfate. The solution was evaporated under reduced pressure, and the residue was subjected to column chromatography on silica gel (200 g) with a mixture of chloroform and methanol (20:1). The eluate was evaporated in vacuo to give powder [3.1 g] of 2-n-octyloxy-1-n-octyloxymethylethyl 7-[2-(2-formamidothiazol-4-yl)-2-methoxyiminoacetamido]-2-cephem-4-carboxylate (syn isomer).

Workup

  1. stirringstirred at 0° C. for an hour
  2. extractionextracted with ethyl acetate (300 ml)
  3. washThe extract was washed with a saturated aqueous solution of sodium chloride
  4. dry with materialan aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride in turn, and dried over anhydrous magnesium sulfate
  5. customThe solution was evaporated under reduced pressure
  6. additionthe residue was subjected to column chromatography on silica gel (200 g) with a mixture of chloroform and methanol (20:1)
  7. customThe eluate was evaporated in vacuo

Sources & evidence

ORD record
ord-0017c205d8ed4825b31a0652dd58c8da
Source dataset
uspto-grants-1984_10
Patent number
US04477447

Reaction notes

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