Acetamide, N-(trimethylsilyl)- → Benzhydryl 7-[2-(2-tritylaminothiazol-4-yl)-2-difluoromethoxyiminoacetamido]-3-chloromethyl-3-cephem-4-carboxylate

HRID 34495Notes

Reaction equation

HRID 34495 reaction equation
[C:1]([NH:20][C:21]1[S:22][CH:23]=[C:24]([C:26](=[N:30][O:31][CH:32]([F:34])[F:33])[C:27](O)=[O:28])[N:25]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.S(Cl)(C)(=O)=O.[NH2:49][CH:50]1[C:75](=[O:76])[N:52]2[C:53]([C:59]([O:61][CH:62]([C:69]3[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=3)[C:63]3[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=3)=[O:60])=[C:54]([CH2:57][Cl:58])[CH2:55][S:56][C@H:51]12.C[Si](C)(C)NC(=O)C>CN(C)C=O.C(Cl)Cl.O>[C:1]([NH:20][C:21]1[S:22][CH:23]=[C:24]([C:26](=[N:30][O:31][CH:32]([F:33])[F:34])[C:27]([NH:49][CH:50]2[C:75](=[O:76])[N:52]3[C:53]([C:59]([O:61][CH:62]([C:63]4[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=4)[C:69]4[CH:70]=[CH:71][CH:72]=[CH:73][CH:74]=4)=[O:60])=[C:54]([CH2:57][Cl:58])[CH2:55][S:56][C@H:51]23)=[O:28])[N:25]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 5

HCID 25989Acetamide, N-(trimethylsilyl)-HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 13239626Benzhydryl 7-Amino-3-chloromethyl-3-cephem-4-carboxylateHCID 536668022-(2-Tritylamino-4-thiazolyl)-2-difluoromethoxyimino-acetic acid

Product 1

HCID 131715668Benzhydryl 7-[2-(2-tritylaminothiazol-4-yl)-2-difluoromethoxyiminoacetamido]-3-chloromethyl-3-cephem-4-carboxylateYield 105.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-30 °C

Procedure

A mixture of 2-(2-tritylaminothiazol-4-yl)-2-difluoromethoxyiminoacetic acid (syn isomer) (2.4 g) and diisopropylethylamine (1.29 g) in N,N-dimethylformamide (35 ml) was cooled to -30° C. and mesyl chloride (1.15 g) was added dropwise thereto. The mixture was stirred at -20° to -30° C. for 30 minutes to give an activated acid solution. On the other hand, a mixture of benzhydryl 7-amino-3-chloromethyl-3-cephem-4-carboxylate (2.18 g) and N-trimethylsilylacetamide (5.25 g) in methylene chloride (20 ml) was stirred to be a clear solution for 30 minutes at room temperature and then cooled to -20° C. To this solution was added the activated acid solution obtained above in one portion. The mixture was stirred for 30 minutes at -15° to -10° C., poured into water and extracted with ethyl acetate. The extract was washed with water three times, dried over magnesium sulfate and evaporated under reduced pressure. The residue was triturated in diisopropyl ether to give benzhydryl 7-[2-(2-tritylaminothiazol-4-yl)- 2-difluoromethoxyiminoacetamido]-3-chloromethyl-3-cephem-4-carboxylate (syn isomer) (4.64 g).

Workup

  1. customto give an activated acid solution
  2. stirringwas stirred
  3. customfor 30 minutes
  4. customat room temperature
  5. temperaturecooled to -20° C
  6. additionTo this solution was added the activated acid solution
  7. customobtained above in one portion
  8. stirringThe mixture was stirred for 30 minutes at -15° to -10° C.
  9. extractionextracted with ethyl acetate
  10. washThe extract was washed with water three times
  11. dry with materialdried over magnesium sulfate
  12. customevaporated under reduced pressure
  13. customThe residue was triturated in diisopropyl ether

Sources & evidence

ORD record
ord-6287db9a63924f7c97382e0d932bd071
Source dataset
uspto-grants-1988_08
Patent number
US04761410

Reaction notes

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