Hydrochloric Acid → p-Nitrobenzyl 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetamido]-3-vinylthio-3-cephem-4-carboxylate

HRID 704279Notes

Reaction equation

HRID 704279 reaction equation
C(N[CH:5]([CH3:7])C)(C)C.C([Li])CCC.C(OC1[S:20]CCO1)C.[NH2:21][C:22]1[S:26][N:25]=[C:24]([C:27](=[N:58][O:59][CH2:60][CH3:61])[C:28]([NH:30][CH:31]2[C:56](=[O:57])[N:33]3[C:34]([C:43]([O:45][CH2:46][C:47]4[CH:52]=[CH:51][C:50]([N+:53]([O-:55])=[O:54])=[CH:49][CH:48]=4)=O)=[C:35](OS(C)(=O)=O)[CH2:36][S:37][C@H:32]23)=[O:29])[N:23]=1.Cl>O1CCCC1.CCCCCC>[NH2:21][C:22]1[S:26][N:25]=[C:24]([C:27](=[N:58][O:59][CH2:60][CH3:61])[C:28]([NH:30][CH:31]2[C:56](=[O:57])[N:33]3[C:34]([C:43]([O:45][CH2:46][C:47]4[CH:48]=[CH:49][C:50]([N+:53]([O-:55])=[O:54])=[CH:51][CH:52]=4)=[S:20])=[C:35]([CH:5]=[CH2:7])[CH2:36][S:37][C@H:32]23)=[O:29])[N:23]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 7912DiisopropylamineHCID 51360032-Ethoxy-1,3-oxathiolaneHCID 131716148p-Nitrobenzyl 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetamido]-3-mesyloxy-3-cephem-4-carboxylateHCID 178418339Butyllithium

Product 1

HCID 131716166p-Nitrobenzyl 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetamido]-3-vinylthio-3-cephem-4-carboxylate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of N,N-diisopropylamine (0.65 ml) in tetrahydrofuran (7 ml) was added 1.55M n-butyllithium in n-hexane (2.88 ml) at -20°~-15° C. The mixture was stirred for 30 minutes at 0° C. To the solution was added a solution of 2-ethoxy-1,3-oxathiolane (642 mg) in tetrahydrofuran (2 ml) at -60° C., and the resultant mixture was stirred for 30 minutes at the same temperature. The solution was added to a solution of p-nitrobenzyl 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetamido]-3-mesyloxy-3-cephem-4-carboxylate (syn isomer) (2 g) in tetrahydrofuran (30 ml) at -62° C. After the mixture was stirred for 15 minutes at the same temperature, 1N hydrochloric acid (5 ml) was added thereto. The mixture was allowed to warm up till 0° C. and extracted with ethyl acetate. The extract was washed with water, dried over magnesium sulfate and concentrated in vacuo. The residue was subjected to column chromatography on silica gel and eluted with a mixture of ethyl acetate and chloroform (1:2). The fractions containing the object compound were combined and concentrated in vacuo to give p-nitrobenzyl 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetamido]-3-vinylthio-3-cephem-4-carboxylate (syn isomer) (805 mg).

Workup

  1. additionwas added
  2. temperatureto warm up till 0° C.
  3. extractionextracted with ethyl acetate
  4. washThe extract was washed with water
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. washeluted with a mixture of ethyl acetate and chloroform (1:2)
  8. additionThe fractions containing the object compound
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4ef68b9063724738bdbc942ed64b4785
Source dataset
uspto-grants-1991_01
Patent number
US04985555

Reaction notes

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