Ethyl Acetate → Pivaloyloxymethyl 2-methyl-7-[2-methoxyimino-2-(2-aminothiazol-4-yl)acetamido]-3-cephem-4-carboxylate

HRID 28299

Reaction equation

HRID 28299 reaction equation
[CH3:1][CH:2]1[CH:7]=[C:6]([C:8]([O-:10])=[O:9])[N:5]2[C:11](=[O:26])[CH:12]([NH:13][C:14](=[O:25])[C:15](=[N:22][O:23][CH3:24])[C:16]3[NH:17][C:18](=[NH:21])[S:19][CH:20]=3)[C@H:4]2[S:3]1.[Na+].[C:28]([O:34][CH2:35]I)(=[O:33])[C:29]([CH3:32])([CH3:31])[CH3:30].C(OCC)(=O)C>CN(C)C=O>[CH3:1][CH:2]1[CH:7]=[C:6]([C:8]([O:10][CH2:35][O:34][C:28](=[O:33])[C:29]([CH3:32])([CH3:31])[CH3:30])=[O:9])[N:5]2[C:11](=[O:26])[CH:12]([NH:13][C:14](=[O:25])[C:15](=[N:22][O:23][CH3:24])[C:16]3[N:17]=[C:18]([NH2:21])[S:19][CH:20]=3)[C@H:4]2[S:3]1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 104401Iodomethyl pivalateHCID 178502771HCID 178502771, compound

Product 1

HCID 131711501Pivaloyloxymethyl 2-methyl-7-[2-methoxyimino-2-(2-aminothiazol-4-yl)acetamido]-3-cephem-4-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of 2-methyl-7-[2-methoxyimino-2-(2-aminothiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid (syn isomer), which can be represented as 2-methyl-7-[2-methoxyimino-2-(2-imino-2,3-dihydrothiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid (syn isomer), (4.8 g.) in water (48 ml.) was added dropwise 1 N aqueous sodium hydroxide solution at the rate that the pH value of the mixture was not more than 7. The mixture was filtered and then lyophilized to give sodium 2-methyl-7-[2-methoxyimino-2-(2-aminothiazol-4-yl)acetamido]-3-cephem-4-carboxylate (syn isomer), which can be represented as sodium 2-methyl-7-[2-methoxyimino-2-(2-imino-2,3-dihydrothiazol-4-yl)acetamido]-3-cephem-4-carboxylate (syn isomer), (4.8 g.), mp>250° C. This compound is suspended in dried dimethylformamide (20 ml.), and to the suspension was added iodomethyl pivalate (2.30 g.) with vigorous stirring under cooling to 3° to 5° C., and then the mixture was stirred for 20 minutes at the same temperature. The reaction mixture was poured into a mixture of ethyl acetate (60 ml.) and ice-water (10 ml.), and the mixture was well shaken. The ethyl acetate layer was separated, washed with a saturated aqueous sodium bicarbonate solution, water and a saturated aqueous sodium chloride solution in turn. After the ethyl acetate layer was dried over magnesium sulfate, ethyl acetate was distilled off under reduced pressure. The residual oil was pulverized in diethyl ether (25 ml.), collected by filtration and then dried to give pivaloyloxymethyl 2-methyl-7-[2-methoxyimino-2-(2-aminothiazol-4-yl)acetamido]-3-cephem-4-carboxylate (syn isomer), which can be represented as pivaloyloxymethyl 2-methyl-7-[2-methoxyimino-2-(2-imino-2,3-dihydrothiazol-4-yl)acetamido]-3-cephem-4-carboxylate (syn isomer), (1.44 g.), mp 165° to 170° C. (dec.).

Workup

  1. temperatureunder cooling to 3° to 5° C.
  2. stirringthe mixture was stirred for 20 minutes at the same temperature
  3. stirringthe mixture was well shaken
  4. customThe ethyl acetate layer was separated
  5. washwashed with a saturated aqueous sodium bicarbonate solution, water
  6. dry with materialAfter the ethyl acetate layer was dried over magnesium sulfate, ethyl acetate
  7. distillationwas distilled off under reduced pressure
  8. filtrationcollected by filtration
  9. customdried

Sources & evidence

ORD record
ord-372df0de5d5640f48b92771b27659de2
Source dataset
uspto-grants-1980_09
Patent number
US04225707

Linked notes

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