Dimethylformamide → HCID 131712594, compound

HRID 1659768Notes

Reaction equation

HRID 1659768 reaction equation
[CH3:1][N:2]([CH3:5])[CH:3]=O.P(Cl)(Cl)([Cl:8])=O.[CH3:11][S:12][CH2:13][O:14][N:15]=[C:16]([C:20]1[N:21]=[C:22]([NH:25][CH:26]=[O:27])[S:23][CH:24]=1)[C:17]([OH:19])=O.[NH2:28][CH:29]1[C:46](=[O:47])[N:31]2[C:32]([C:43]([OH:45])=[O:44])=[C:33]([CH2:36][S:37][C:38]3[S:39][CH:40]=[N:41][N:42]=3)[CH2:34][S:35][C@H:30]12>O.CC(C)=O.C(N(CC)CC)C.O1CCCC1>[CH3:1][N+:2]([CH3:5])=[CH:3][Cl:8].[Cl-:8].[CH3:11][S:12][CH2:13][O:14][N:15]=[C:16]([C:20]1[N:21]=[C:22]([NH:25][CH:26]=[O:27])[S:23][CH:24]=1)[C:17]([NH:28][CH:29]1[C:46](=[O:47])[N:31]2[C:32]([C:43]([OH:45])=[O:44])=[C:33]([CH2:36][S:37][C:38]3[S:39][CH:40]=[N:41][N:42]=3)[CH2:34][S:35][C@H:30]12)=[O:19]

Participants

10

Reactant 4

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 128891877-Amino-3-(1,3,4-thiadiazol-2-ylthiomethyl)-3cephem-4-carboxylic acidHCID 53744847HCID 53744847, compound

Product 2

HCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 131712594HCID 131712594, compoundYield 115.2%

Reagents, catalysts & solvents 4

HCID 180AcetoneSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolvent

Procedure

The Vilsmeier reagent was prepared from dry dimethylformamide (0.139 g.), phosphorus oxychloride (0.290 g.) and dry tetrahydrofuran (1.0 ml.) by the conventional method. Dry tetrahydrofuran (3.0 ml.) was added thereto and then 2-methylthiomethoxyimino-2-(2-formamidothiazol-4-yl)acetic acid (syn isomer) (0.4 g.) was added thereto at -5° to 0° C. The mixture was stirred for 30 minutes at the same temperature. The resulting mixture was dropwise added at -5° to 0° C. to a stirred solution of 7-amino-3-(1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (0.725 g.) in a mixture of water (7 ml.) and acetone (7 ml.) keeping the pH at 7.5 to 8.5 by triethylamine and the mixture was stirred for 30 minutes at the same temperature at pH 7.5 to 8.5. Acetone was removed from the reaction mixture. To the residue were added ethyl acetate and water and the mixture was adjusted to pH 2.0 with 10% hydrochloric acid. Insoluble material was filtered off and the filtrate was extracted twice with ethyl acetate. The combined extracts were washed twice with a saturated sodium chloride aqueous solution and dried over magnesium sulfate. The solvent was distilled off and the residue was pulverized with diethyl ether to give 7-[2-methylthiomethoxyimino-2-(2-formamidothiazol-4-yl)acetamido]-3-(1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer) (0.64 g.).

Workup

  1. customat -5° to 0° C
  2. stirringthe mixture was stirred for 30 minutes at the same temperature at pH 7.5 to 8.5
  3. customAcetone was removed from the reaction mixture
  4. additionTo the residue were added ethyl acetate and water
  5. filtrationInsoluble material was filtered off
  6. extractionthe filtrate was extracted twice with ethyl acetate
  7. washThe combined extracts were washed twice with a saturated sodium chloride aqueous solution
  8. dry with materialdried over magnesium sulfate
  9. distillationThe solvent was distilled off

Sources & evidence

ORD record
ord-179b17f994be410d951a9c854c9ac4b2
Source dataset
uspto-grants-1981_12
Patent number
US04304770

Reaction notes

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