Phosphorus oxychloride → Benzhydryl 7-[2-(2-methanesulfonamidothiazol-4-yl)acetamido]-3-vinyl-3-cephem-4-carboxylate

HRID 1088123Notes

Reaction equation

HRID 1088123 reaction equation
[CH3:1][S:2]([NH:5][C:6]1[S:7][CH:8]=[C:9]([CH2:11][C:12]([OH:14])=O)[N:10]=1)(=[O:4])=[O:3].P(Cl)(Cl)(Cl)=O.Cl.[NH2:21][CH:22]1[C:47](=[O:48])[N:24]2[C:25]([C:31]([O:33][CH:34]([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)=[O:32])=[C:26]([CH:29]=[CH2:30])[CH2:27][S:28][C@H:23]12.C[Si](CC(N)=O)(C)C.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C.O1CCCC1.O.CN(C)C=O>[CH3:1][S:2]([NH:5][C:6]1[S:7][CH:8]=[C:9]([CH2:11][C:12]([NH:21][CH:22]2[C:47](=[O:48])[N:24]3[C:25]([C:31]([O:33][CH:34]([C:35]4[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=4)[C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=4)=[O:32])=[C:26]([CH:29]=[CH2:30])[CH2:27][S:28][C@H:23]23)=[O:14])[N:10]=1)(=[O:3])=[O:4]

Participants

10

Reactant 5

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 516892Sodium BicarbonateHCID 31595752-(2-Methanesulfonamido-1,3-thiazol-4-yl)acetic acidHCID 12818005Benzhydryl 7-amino-3vinyl-3cephem-4-carboxylate hydrochloride

Product 1

HCID 88469469Benzhydryl 7-[2-(2-methanesulfonamidothiazol-4-yl)acetamido]-3-vinyl-3-cephem-4-carboxylateYield 58.8%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent3×

Procedure

A mixture of 2-(2-methanesulfonamidothiazol-4-yl)acetic acid (2.6 g), N,N-dimethylformamide (0.88 g) and phosphorus oxychloride (1.85 g) in ethyl acetate (10 ml) and tetrahydrofuran (20 ml) was stirred under ice-cooling for 30 minutes. This solution was added to a solution of benzhydryl 7-amino-3-vinyl-3-cephem-4-carboxylate hydrochloride (4.3 g) and trimethylsilylacetamide (7.9 g) in ethyl acetate (50 ml) at -20° C. with stirring, and the stirring was continued at -20° to 0° C. for 2 hours. After addition of water, tetrahydrofuran and ethyl acetate, the reaction mixture was adjusted to pH 7 with a saturated aqueous solution of sodium bicarbonate. The precipitated substance was collected by filtration to give benzhydryl 7-[2-(2-methanesulfonamidothiazol-4-yl)acetamido]-3-vinyl-3-cephem-4-carboxylate (3.6 g). After addition of ethyl acetate tetrahydrofuran to the filtrate, the organic layer was separated out, washed with an aqueous solution of sodium chloride and then dried over anhydrous magnesium sulfate, followed by evaporation to recover the same product (0.9 g). Total yield: 4.5 g.

Workup

  1. temperaturecooling for 30 minutes
  2. stirringwith stirring
  3. filtrationThe precipitated substance was collected by filtration

Sources & evidence

ORD record
ord-d77ca055ee45412282a7d7001727fbf2
Source dataset
uspto-grants-1990_10
Patent number
US04960889

Reaction notes

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