N,N-Dimethylaniline → Benzhydryl 7-[2-(2-tritylaminothiazol-4-yl)-2-difluoromethoxyiminoacetamido]-3-(1-methyl-1-pyrrolidiniomethyl)-3-cephem-4-carboxylate iodide

HRID 34505Notes

Reaction equation

HRID 34505 reaction equation
[I-:1].[C:2]([NH:21][C:22]1[S:23][CH:24]=[C:25]([C:27](=[N:64][O:65][CH:66]([F:68])[F:67])[C:28]([NH:30][CH:31]2[C:62](=[O:63])[N:33]3[C:34]([C:46]([O:48][CH:49]([C:56]4[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=4)[C:50]4[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=4)=[O:47])=[C:35]([CH:39]([CH3:45])[NH+:40]4[CH2:44][CH2:43][CH2:42][CH2:41]4)[CH2:36][S:37](=O)[C@H:32]23)=[O:29])[N:26]=1)([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.CN(C)C1C=CC=CC=1.P(Cl)(Cl)Cl.C(OC(C)C)(C)C>C(#N)C>[I-:1].[C:2]([NH:21][C:22]1[S:23][CH:24]=[C:25]([C:27](=[N:64][O:65][CH:66]([F:67])[F:68])[C:28]([NH:30][CH:31]2[C:62](=[O:63])[N:33]3[C:34]([C:46]([O:48][CH:49]([C:50]4[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=4)[C:56]4[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=4)=[O:47])=[C:35]([CH:39]([CH3:45])[NH+:40]4[CH2:41][CH2:42][CH2:43][CH2:44]4)[CH2:36][S:37][C@H:32]23)=[O:29])[N:26]=1)([C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

6

Reactant 4

HCID 949N,N-DimethylanilineHCID 7914Diisopropyl EtherHCID 24387Phosphorus trichlorideHCID 131715681Benzhydryl 7-[2-(2-tritylaminothiazol-4-yl)-2-difluoromethoxyiminoacetamido]-3-(1-methyl-1-pyrrolidiniomethyl)-3-cephem-4-carboxylate-1-oxide iodide

Product 1

HCID 131715685Benzhydryl 7-[2-(2-tritylaminothiazol-4-yl)-2-difluoromethoxyiminoacetamido]-3-(1-methyl-1-pyrrolidiniomethyl)-3-cephem-4-carboxylate iodide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of benzhydryl 7-[2-(2-tritylaminothiazol-4-yl)-2-difluoromethoxyiminoacetamido]-3-(1-methyl-1-pyrrolidiniomethyl)-3-cephem-4-carboxylate-1-oxide iodide (syn isomer) (1.45 g) and acetonitrile (14 ml) was stirred under cooling in an ice-bath, and N,N-dimethylaniline (490 mg) and phosphorus trichloride (555 mg) were added thereto. The mixture was stirred for one hour under cooling in an ice-bath, and then diisopropyl ether was added to the reaction mixture. The separated oil was triturated with diisopropyl ether to give benzhydryl 7-[2-(2-tritylaminothiazol-4-yl)-2-difluoromethoxyiminoacetamido]-3-(1-methyl-1-pyrrolidiniomethyl)-3-cephem-4-carboxylate iodide. This compound was dissolved in a solution of tetrahydrofuran (54 ml) and water (3.6 ml). The solution was subjected to column chromatography on Amberlite IRA-400 (CF3COO⃝ form) and the elution was carried out with a solution of water and tetrahydrofuran (1:15). The fractions containing the object compound were collected and evaporated. The residue was triturated with diisopropyl ether to give benzhydryl 7-[ 2-(2-tritylaminothiazol-4-yl)-2-difluoromethoxyiminoacetamido]-3-(1-methyl-1-pyrrolidiniomethyl)-3-cephem-4-carboxylate trifluoroacetate (syn isomer) (1.30 g).

Workup

  1. temperatureunder cooling in an ice-bath
  2. stirringThe mixture was stirred for one hour
  3. temperatureunder cooling in an ice-bath
  4. customThe separated oil was triturated with diisopropyl ether

Sources & evidence

ORD record
ord-8666edd5dba74671a3f5ad7f81481cfc
Source dataset
uspto-grants-1988_08
Patent number
US04761410

Reaction notes

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