Water → N-(1,4,5a,6-Tetrahydro-3-hydroxy-1,7-dioxo-3H,7H-azeto[2,1-b]furo[3,4-d][1,3]thiazin-6-yl)-2-(2-tritylaminothiazol-4-yl)-2-methoxyiminoacetic acid amide

HRID 2250821Notes

Reaction equation

HRID 2250821 reaction equation
[NH2:1][C@@H:2]1[C:9](=[O:10])[N:8]2[C@@H:3]1[S:4][CH2:5][C:6]([CH:14]=[O:15])=[C:7]2[C:11]([OH:13])=[O:12].C/C(/O[Si](C)(C)C)=N\[Si](C)(C)C.[C:28]([NH:47][C:48]1[S:49][CH:50]=[C:51](/[C:53](=[N:57]/[O:58][CH3:59])/[C:54](Cl)=[O:55])[N:52]=1)([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.O>C(#N)C.C(Cl)Cl>[OH:15][CH:14]1[C:6]2[CH2:5][S:4][CH:3]3[CH:2]([NH:1][C:54](=[O:55])[C:53]([C:51]4[N:52]=[C:48]([NH:47][C:28]([C:35]5[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=5)([C:29]5[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=5)[C:41]5[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=5)[S:49][CH:50]=4)=[N:57][O:58][CH3:59])[C:9](=[O:10])[N:8]3[C:7]=2[C:11](=[O:13])[O:12]1

Participants

6

Reactant 4

HCID 962WaterHCID 6913588N,O-bis(trimethylsilyl)acetamideHCID 12881254(2Z)-2-methoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl chlorideHCID 15385898(6R,7R)-7-amino-3-formyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Product 1

HCID 54423694N-(1,4,5a,6-Tetrahydro-3-hydroxy-1,7-dioxo-3H,7H-azeto[2,1-b]furo[3,4-d][1,3]thiazin-6-yl)-2-(2-tritylaminothiazol-4-yl)-2-methoxyiminoacetic acid amide

Reagents, catalysts & solvents 1

HCID 21877088Acetonitrile methylene chlorideSolvent

Procedure

10 g of 7-amino-3-formyl-3-cephem-4-carboxylic acid in 200 ml of acetonitrile: methylenchloride (1:1) are treated with 37.4 ml of N,O-bis(trimethylsilyl)acetamide at room temperature within ca. 5 minutes. After ca. 30 minutes the reaction mixture is cooled to −10° and 21 g of 2-(2-tritylaminothiazol-4-yl)-(Z)-2-methoxyiminoacetic acid chloride are added in 3 portions. The temperature raises to −5°. After ca. 45 minutes the reaction mixture is treated with 4 ml of water. The temperature raises to 20°. The reaction mixture is stirred for ca. 10 minutes and filtered. 15 g of active charcoal are added to this filtrate and stirring is continued for ca. 10 minutes. After filtration the solvent of the filtrate obtained is evaporated. The evaporation residue is treated with tert.butyl-methyl ether. A crystalline, almost colourless precipitate is obtained, filtered off and dried. Crystalline N-(1,4,5a,6-Tetrahydro-3-hydroxy-1,7-dioxo-3H,7H-azeto[2,1-b]furo[3,4-d][1,3]thiazin-6-yl)-2-(2-tritylaminothiazol-4-yl)-2-methoxyiminoacetic acid amide is obtained in form of a diastereomeric mixture in the ratio of ca. 1:1.

Workup

  1. temperatureAfter ca. 30 minutes the reaction mixture is cooled to −10°
  2. temperatureThe temperature raises to −5°
  3. temperatureThe temperature raises to 20°
  4. filtrationfiltered
  5. addition15 g of active charcoal are added to this filtrate
  6. stirringstirring
  7. waitis continued for ca. 10 minutes
  8. filtrationAfter filtration the solvent of the filtrate
  9. customobtained
  10. customis evaporated
  11. additionThe evaporation residue is treated with tert.butyl-methyl ether
  12. customA crystalline, almost colourless precipitate is obtained
  13. filtrationfiltered off
  14. customdried

Sources & evidence

ORD record
ord-d50a10cd7b2b4d82b8118e5daba2ee6d
Source dataset
uspto-grants-2008_01
Patent number
US07317101B2

Reaction notes

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