2,6-Lutidine → Benzhydryl 7-[2-(2-formamidothiazol-4-yl)acetamido]-3-(4-methyl-1-piperazinyl)carbonyloxymethyl-3-cephem-4-carboxylate-1-oxide

HRID 434870Notes

Reaction equation

HRID 434870 reaction equation
[CH:1]([NH:3][C:4]1[S:5][CH:6]=[C:7]([CH2:9][C:10]([OH:12])=O)[N:8]=1)=[O:2].N1C(C)=CC=CC=1C.C(Cl)(=O)C(C)(C)C.[NH2:28][CH:29]1[C:64](=[O:65])[N:31]2[C:32]([C:48]([O:50][CH:51]([C:58]3[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=3)[C:52]3[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=3)=[O:49])=[C:33]([CH2:37][O:38][C:39]([N:41]3[CH2:46][CH2:45][N:44]([CH3:47])[CH2:43][CH2:42]3)=[O:40])[CH2:34][S:35](=[O:36])[C@H:30]12>C(Cl)Cl.C(N(CC)CC)C>[CH:1]([NH:3][C:4]1[S:5][CH:6]=[C:7]([CH2:9][C:10]([NH:28][CH:29]2[C:64](=[O:65])[N:31]3[C:32]([C:48]([O:50][CH:51]([C:58]4[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=4)[C:52]4[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=4)=[O:49])=[C:33]([CH2:37][O:38][C:39]([N:41]4[CH2:46][CH2:45][N:44]([CH3:47])[CH2:43][CH2:42]4)=[O:40])[CH2:34][S:35](=[O:36])[C@H:30]23)=[O:12])[N:8]=1)=[O:2]

Participants

7

Reactant 4

HCID 79372,6-LutidineHCID 62493Pivaloyl chlorideHCID 112868864-Thiazoleacetic acid, 2-(formylamino)-HCID 70526114Benzhydryl 7-amino-3-(4-methyl-1-piperazinyl)carbonyloxymethyl-3-cephem-4-carboxylate-1-oxide

Product 1

HCID 88733248Benzhydryl 7-[2-(2-formamidothiazol-4-yl)acetamido]-3-(4-methyl-1-piperazinyl)carbonyloxymethyl-3-cephem-4-carboxylate-1-oxideYield 78.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Conditions

Temperature
22 °C

Procedure

A mixture of 2-(2-formamidothiazol-4-yl)acetic acid (0.70 g), 2,6-lutidine (0.44 ml), triethylamine (0.05 ml) and pivaloyl chloride (457 mg) in dry methylene chloride (10 ml) was stirred at -15° C. for 20 minutes, at 12° C. for 20 minutes and at 22° C. for a further 40 minutes. A mixture of benzhydryl 7-amino-3-(4-methyl-1-piperazinyl)carbonyloxymethyl-3-cephem-4-carboxylate-1-oxide (1.7 g) in methylene chloride (20 ml) was cooled to -30° C. and thereto was added the acid anhydride solution obtained above followed by stirring at -20° to -10° C. for an hour and at -10° C. to ambient temperature for a further one hour. The reaction mixture was evaporated and to the residue was added ethyl acetate (20 ml) and water (10 ml) followed by stirring. Insoluble substances were collected by filtration, washed with water and ethyl acetate and then dried under reduced pressure to give benzhydryl 7-[2-(2-formamidothiazol-4-yl)acetamido]-3-(4-methyl-1-piperazinyl)carbonyloxymethyl-3-cephem-4-carboxylate-1-oxide (1.75 g).

Workup

  1. temperaturewas cooled to -30° C.
  2. customobtained
  3. stirringby stirring at -20° to -10° C. for an hour and at -10° C. to ambient temperature for a further one hour
  4. customThe reaction mixture was evaporated and to the residue
  5. additionwas added ethyl acetate (20 ml) and water (10 ml)
  6. stirringby stirring
  7. filtrationInsoluble substances were collected by filtration
  8. washwashed with water and ethyl acetate
  9. customdried under reduced pressure

Sources & evidence

ORD record
ord-2a0fc05739b148aeb760c73003d904dd
Source dataset
uspto-grants-1983_08
Patent number
US04399278

Reaction notes

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