Sodium Carbonate → Tert-butyl 7-[2-(2-formamidothiazol-4-yl)-2-methoxyiminoacetamido]-3-methoxymethyl-3-cephem-4-carboxylate

HRID 234185Notes

Reaction equation

HRID 234185 reaction equation
S(C1C=CC(C)=CC=1)(O)(=O)=O.[NH2:12][CH:13]1[C:30](=[O:31])[N:15]2[C:16]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[C:17]([CH2:20][O:21][CH3:22])[CH2:18][S:19][C@H:14]12.C(=O)(O)[O-].[Na+].[CH:37]([NH:39][C:40]1[S:41][CH:42]=[C:43]([C:45](=[N:49][O:50][CH3:51])[C:46](O)=[O:47])[N:44]=1)=[O:38].P(Cl)(Cl)(Cl)=O.C(=O)([O-])[O-].[Na+].[Na+]>CC(C)=O.O1CCCC1.O.CN(C)C=O>[CH:37]([NH:39][C:40]1[S:41][CH:42]=[C:43]([C:45](=[N:49][O:50][CH3:51])[C:46]([NH:12][CH:13]2[C:30](=[O:31])[N:15]3[C:16]([C:23]([O:25][C:26]([CH3:27])([CH3:28])[CH3:29])=[O:24])=[C:17]([CH2:20][O:21][CH3:22])[CH2:18][S:19][C@H:14]23)=[O:47])[N:44]=1)=[O:38]

Participants

10

Reactant 5

HCID 10340Sodium CarbonateHCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 27245112-(2-Formylamino-1,3-Thiazol-4-Yl)-2-(Methoxyimino)Acetic AcidHCID 131713144Tert-butyl 7-amino-3-methoxymethyl-3-cephem-4-carboxylate tosylate

Product 1

HCID 131713145Tert-butyl 7-[2-(2-formamidothiazol-4-yl)-2-methoxyiminoacetamido]-3-methoxymethyl-3-cephem-4-carboxylateYield 52.7%

Reagents, catalysts & solvents 4

HCID 180AcetoneSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

tert-Butyl 7-amino-3-methoxymethyl-3-cephem-4-carboxylate tosylate (2.0 g) was dissolved in a mixture of acetone (40 ml) and a saturated aqueous solution of sodium bicarbonate (15 ml), and thereto was added dropwise a solution of the activated acid, which was prepared from 2-(2-formamidothiazol-4-yl)-2-methoxyiminoacetic acid (syn isomer) (1.06 g), phosphorus oxychloride (0.85 g) and N,N-dimethylformamide (0.41 g) in tetrahydrofuran (10 ml), at 0° to 5° C. over a period of 10 minutes. During the addition, the pH value of the reaction mixture was maintained at pH 7.0 to 7.5 with a saturated aqueous solution of sodium carbonate. After stirring for an hour, the reaction mixture was diluted with water (50 ml), followed by extracting twice with ethyl acetate. The combined extract was washed with 5% aqueous solution of sodium bicarbonate and water, dried and then evaporated to dryness under reduced pressure to give a residue, which was triturated with diethyl ether to obtain tert-butyl 7-[2-(2-formamidothiazol-4-yl)-2-methoxyiminoacetamido]-3-methoxymethyl-3-cephem-4-carboxylate (syn isomer) (1.14 g).

Workup

  1. additionDuring the addition
  2. extractionby extracting twice with ethyl acetate
  3. extractionThe combined extract
  4. washwas washed with 5% aqueous solution of sodium bicarbonate and water
  5. customdried
  6. customevaporated to dryness under reduced pressure
  7. customto give a residue, which
  8. customwas triturated with diethyl ether

Sources & evidence

ORD record
ord-1cd08bb9823e4e0ba9154303f9931f96
Source dataset
uspto-grants-1997_01
Patent number
US05594132

Reaction notes

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