Trifluoroacetic acid → 7-[2-Carboxymethoxyimino-2-(1,2,4-thiadiazol-3-yl)acetamido]3-(tetrazolo[1,5-b]pyridazin-6-yl)thiomethyl-3-cephem-4-carboxylic acid

HRID 1463072Notes

Reaction equation

HRID 1463072 reaction equation
FC(F)(F)C(O)=O.C([O:12][C:13]([CH2:15][O:16][N:17]=[C:18]([C:45]1[N:49]=[CH:48][S:47][N:46]=1)[C:19]([NH:21][CH:22]1[C:43](=[O:44])[N:24]2[C:25]([C:40]([OH:42])=[O:41])=[C:26]([CH2:29][S:30][C:31]3[CH:32]=[CH:33][C:34]4[N:35]([N:37]=[N:38][N:39]=4)[N:36]=3)[CH2:27][S:28][C@H:23]12)=[O:20])=[O:14])(C)(C)C.C(OC(C)C)(C)C>C(Cl)Cl.C1(OC)C=CC=CC=1>[C:13]([CH2:15][O:16][N:17]=[C:18]([C:45]1[N:49]=[CH:48][S:47][N:46]=1)[C:19]([NH:21][CH:22]1[C:43](=[O:44])[N:24]2[C:25]([C:40]([OH:42])=[O:41])=[C:26]([CH2:29][S:30][C:31]3[CH:32]=[CH:33][C:34]4[N:35]([N:37]=[N:38][N:39]=4)[N:36]=3)[CH2:27][S:28][C@H:23]12)=[O:20])([OH:14])=[O:12]

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7914Diisopropyl EtherHCID 1317136127-[2-t-Butoxycarbonylmethoxyimino-2-(1,2,4-thiadiazol-3-yl)acetamido]-3-(tetrazolo[1,5-b]pyridazin-6-yl)thiomethyl-3-cephem-4-carboxylic acid

Product 1

HCID 1317136137-[2-Carboxymethoxyimino-2-(1,2,4-thiadiazol-3-yl)acetamido]3-(tetrazolo[1,5-b]pyridazin-6-yl)thiomethyl-3-cephem-4-carboxylic acidYield 21.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 7519AnisoleSolvent

Procedure

Trifluoroacetic acid (12 ml) was added to a suspension of 7-[2-t-butoxycarbonylmethoxyimino-2-(1,2,4-thiadiazol-3-yl)acetamido]-3-(tetrazolo[1,5-b]pyridazin-6-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer) (4 g) in methylene chloride (8 ml) and anisole (4 ml) at ambient temperature and the solution was stirred for 1.5 hours at the same temperature. To the resulting solution was added diisopropyl ether under stirring. The precipitates were collected by filtration, washed with diisopropyl ether. The precipitates were added to the mixture of ethyl acetate and water, and the mixture was adjusted to pH 7.5 with 20% aqueous solution of sodium carbonate. The separated aqueous layer was adjusted to pH 5.0 with 10% hydrochloric acid. The resulting solution was subjected to column chromatography on macroporous non-ionic adsorption resin "Diaion HP-20" (Trademark: prepared by Mitsubishi Chemical Industries Ltd.) and eluted with water. The fractions containing the object compound were adjusted to pH 2.0 with 10% hydrochloric acid. The precipitates were collected by filtration, washed with water and dried over phosphorus pentoxide in vacuo to give 7-[2-carboxymethoxyimino-2-(1,2,4-thiadiazol-3-yl)acetamido]3-(tetrazolo[1,5-b]pyridazin-6-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer) (0.77 g).

Workup

  1. stirringunder stirring
  2. filtrationThe precipitates were collected by filtration
  3. washwashed with diisopropyl ether
  4. additionThe precipitates were added to the mixture of ethyl acetate and water
  5. custom" (Trademark: prepared by Mitsubishi Chemical Industries Ltd.)
  6. washeluted with water
  7. additionThe fractions containing the object compound
  8. filtrationThe precipitates were collected by filtration
  9. washwashed with water
  10. dry with materialdried over phosphorus pentoxide in vacuo

Sources & evidence

ORD record
ord-2d198ced8de1485cb87b6793d5dfca98
Source dataset
uspto-grants-1984_07
Patent number
US04463003

Reaction notes

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