Sodium Chloride → (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-trityloxyiminoacetyl]amino]-8-oxo-3-(pyrazin-2-ylmethylsulfanyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

HRID 992702Notes

Reaction equation

HRID 992702 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[C:5](/[C:7](=[N:11]/[O:12][C:13]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)/[C:8](O)=[O:9])[N:6]=1.C(=O)([O-])[O-].[K+].[K+].CS(Cl)(=O)=O.Cl.[NH2:44][C@@H:45]1[C:63](=[O:64])[N:47]2[C:48]([C:60]([OH:62])=[O:61])=[C:49]([S:52][CH2:53][C:54]3[CH:59]=[N:58][CH:57]=[CH:56][N:55]=3)[CH2:50][S:51][C@H:46]12.C[Si](C([Si](C)(C)C)C(N)=O)(C)C.[Na+].[Cl-]>CN(C)C(=O)C.CN(C=O)C>[NH2:1][C:2]1[S:3][CH:4]=[C:5](/[C:7](=[N:11]/[O:12][C:13]([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)/[C:8]([NH:44][C@@H:45]2[C:63](=[O:64])[N:47]3[C:48]([C:60]([OH:62])=[O:61])=[C:49]([S:52][CH2:53][C:54]4[CH:59]=[N:58][CH:57]=[CH:56][N:55]=4)[CH2:50][S:51][C@H:46]23)=[O:9])[N:6]=1

Participants

9

Reactant 6

HCID 5234Sodium ChlorideHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 10117176(Z)-2-(2-Aminothiazol-4-yl)-2-((trityloxy)imino)acetic acidHCID 11708267BistrimethylsilylacetamidHCID 701221327beta-Amino-3-[(pyrazin-2-yl)methylthio]-3-cephem-4-carboxylic acid hydrochloride

Product 1

HCID 88179745(6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-trityloxyiminoacetyl]amino]-8-oxo-3-(pyrazin-2-ylmethylsulfanyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acidYield 110.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
5 °C

Procedure

To a solution of 2-(2-aminothiazol-4-yl)-2-(Z)-(trityloxyimino)acetic acid (3.70 g, 8.61 m mol) in N,N-dimethylacetamide (37 ml) was added potassium carbonate (1.19 g, 8.61 m mol) and methansulfonyl chloride (1.33 ml, 17.2 m mol) at 5° C. The mixture was stirred at 5° C. for 30 minutes. To a solution of 7β-amino-3-[(pyrazin-2-yl)methylthio]-3-cephem-4-carboxylic acid hydrochloride (3.42 g, 8.61 m mol) in DMF (34.2 ml) was added bis(trimethylsilyl)acetamide (14.9 ml, 60.3 m mol), and stirred at 5° C. for 20 minutes. To the solution was added the above-mentioned solution of the activated acid. The mixture was stirred at 5° C. for 1 hour. The reaction mixture was poured into 20% NaCl aq. (350 ml). The precipitates were collected by filtration, washed with water and dried in vacuo to give 7β-[2-(2-aminothiazol-4-yl)-2-(Z)-(trityloxyimino)acetamido]-3-[(pyrazin-2-yl)methylthio]-3-cephem-4-carboxylic acid (6.98 g, 9.49 m mol).

Workup

  1. stirringstirred at 5° C. for 20 minutes
  2. additionTo the solution was added the above-mentioned solution of the activated acid
  3. stirringThe mixture was stirred at 5° C. for 1 hour
  4. filtrationThe precipitates were collected by filtration
  5. washwashed with water
  6. customdried in vacuo

Sources & evidence

ORD record
ord-0c61f05e6e5d4930bb4252c38cd1366e
Source dataset
uspto-grants-2002_10
Patent number
US06468995B1

Reaction notes

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