Sodium Carbonate → Benzhydryl 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetamido]-3-[2-(3-pyridyl)vinyl]-3-cephem-4-carboxylate

HRID 464220Notes

Reaction equation

HRID 464220 reaction equation
[CH:1](=O)[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.[Cl-].[CH:10]([O:23][C:24]([C:26]1[N:31]2[C:32](=[O:48])[CH:33]([NH:34][C:35](=[O:47])[C:36]([C:41]3[N:45]=[C:44]([NH2:46])[S:43][N:42]=3)=[N:37][O:38][CH2:39][CH3:40])[C@H:30]2[S:29][CH2:28][C:27]=1[CH2:49][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)=[O:25])([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C(=O)([O-])[O-].[Na+].[Na+].C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.O.C(OCC)(=O)C>[NH2:46][C:44]1[S:43][N:42]=[C:41]([C:36](=[N:37][O:38][CH2:39][CH3:40])[C:35]([NH:34][CH:33]2[C:32](=[O:48])[N:31]3[C:26]([C:24]([O:23][CH:10]([C:11]4[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=4)[C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)=[O:25])=[C:27]([CH:49]=[CH:1][C:2]4[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=4)[CH2:28][S:29][C@H:30]23)=[O:47])[N:45]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 103713-PyridinecarboxaldehydeHCID 11430Potassium CarbonateHCID 131714367[4-Benzhydryloxycarbonyl-7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetamido]-3-cephem-3-ylmethyl]triphenylphosphonium chloride

Product 1

HCID 131714369Benzhydryl 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetamido]-3-[2-(3-pyridyl)vinyl]-3-cephem-4-carboxylateYield 48.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Nicotinaldehyde (1.1 g) was added to a solution of {4-benzhydryloxycarbonyl-7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetamido]-3-cephem-3-ylmethyl}triphenylphosphonium chloride (syn isomer) (3.0 g) in tetrahydrofuran (30 ml) and water (15 ml) and the solution was adjusted to pH 9.0 with 20% aqueous sodium carbonate. The solution was stirred at ambient temperature for 2 hours under keeping the pH 8.8 to 9.2 with 20% aqueous potassium carbonate. Ethyl acetate and water were added to the resulting solution. The separated organic layer was washed with saturated aqueous sodium chloride and dried over magnesium sulfate. The crude product obtained by concentration was purified by silica gel column chromatography using a mixture of acetone and dichloromethane (rate 1:1) as eluent. The eluted fractions were evaporated to give benzhydryl 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetamido]-3-[2-(3-pyridyl)vinyl]-3-cephem-4-carboxylate (syn isomer) (cis-trans mixture) (1.1 g).

Workup

  1. washThe separated organic layer was washed with saturated aqueous sodium chloride
  2. dry with materialdried over magnesium sulfate
  3. customThe crude product obtained by concentration
  4. customwas purified by silica gel column chromatography
  5. additiona mixture of acetone and dichloromethane (rate 1:1) as eluent
  6. customThe eluted fractions were evaporated

Sources & evidence

ORD record
ord-9f082a8ffc664c818261c18cf156682a
Source dataset
uspto-grants-1985_10
Patent number
US04546101

Reaction notes

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