Phosphorus oxychloride → HCID 131713533, compound

HRID 1262755Notes

Reaction equation

HRID 1262755 reaction equation
C[N+](C)=CCl.[Cl-].P(Cl)(Cl)(Cl)=O.[CH:12]([NH:14][C:15]1[S:16][CH:17]=[C:18]([C:20](=[N:24][O:25][CH2:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C:21]([OH:23])=O)[N:19]=1)=[O:13].[NH2:34][CH:35]1[C:69](=[O:70])[N:37]2[C:38]([C:53]([O:55][CH:56]([C:63]3[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=3)[C:57]3[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=3)=[O:54])=[C:39]([O:42][S:43]([C:46]3[CH:52]=[CH:51][C:49]([CH3:50])=[CH:48][CH:47]=3)(=[O:45])=[O:44])[CH2:40][S:41][C@H:36]12>O1CCCC1.C(Cl)Cl.O.CN(C)C=O>[CH:12]([NH:14][C:15]1[S:16][CH:17]=[C:18]([C:20](=[N:24][O:25][CH2:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C:21]([NH:34][CH:35]2[C:69](=[O:70])[N:37]3[C:38]([C:53]([O:55][CH:56]([C:57]4[CH:58]=[CH:59][CH:60]=[CH:61][CH:62]=4)[C:63]4[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=4)=[O:54])=[C:39]([O:42][S:43]([C:46]4[CH:52]=[CH:51][C:49]([CH3:50])=[CH:48][CH:47]=4)(=[O:44])=[O:45])[CH2:40][S:41][C@H:36]23)=[O:23])[N:19]=1)=[O:13]

Participants

9

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 543909512-t-Butoxycarbonylmethoxyimino-2-(2-formamidothiazol-4-yl)acetic acidHCID 88645023HCID 88645023, compound

Product 1

HCID 131713533HCID 131713533, compoundYield 71.7%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Vilsmeier reagent prepared from phosphorus oxychloride (0.67 ml) and N,N-dimethylformamide (0.57 ml) was suspended in dry tetrahydrofuran (24 ml). To the suspension was added 2-(2-formamidothiazol-4-yl)-2-tert-butoxycarbonylmethoxyiminoacetic acid (syn isomer) (2.4 g) at 0° to 5° C. The solution was stirred at the same temperature for an hour to prepare the activated acid solution. To a solution of benzhydryl 7-amino-3-tosyloxy-3-cephem-4-carboxylate (3.0 g) and monotrimethylsilylacetamide (5.8 g) in methylene chloride (30 ml) was added the activated acid solution obtained above at -20° C. all at once. The reaction mixture was stirred at -10° C. for an hour. The resulting solution was poured into water (100 ml) and extracted with ethyl acetate (100 ml). The separated organic layer was washed with a saturated aqueous solution of sodium bicarbonate, and with a saturated aqueous solution of sodium chloride. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure to give benzhydryl 7-[2-(2-formamidothiazol-4-yl)-2-tert-butoxycarbonylmethoxyiminoacetamido]-3-tosyloxy-3-cephem-4-carboxylate (syn isomer) (3.4 g).

Workup

  1. customto prepare the activated acid solution
  2. customobtained above at -20° C. all at once
  3. stirringThe reaction mixture was stirred at -10° C. for an hour
  4. extractionextracted with ethyl acetate (100 ml)
  5. washThe separated organic layer was washed with a saturated aqueous solution of sodium bicarbonate
  6. dry with materialThe organic layer was dried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-aef216fe974b4b2c8c76469397e66f4f
Source dataset
uspto-grants-1984_06
Patent number
US04452851

Reaction notes

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