Phosphorus oxychloride → HCID 131712610, compound

HRID 1659799Notes

Reaction equation

HRID 1659799 reaction equation
P(Cl)(Cl)([Cl:3])=O.[CH:6]1([O:11][N:12]=[C:13]([C:17]2[N:18]=[C:19]([NH:22][C:23](=[O:28])[C:24]([F:27])([F:26])[F:25])[S:20][CH:21]=2)[C:14]([OH:16])=O)[CH2:10][CH2:9][CH2:8][CH2:7]1.[NH2:29][CH:30]1[C:50](=[O:51])[N:32]2[C:33]([C:47]([OH:49])=[O:48])=[C:34]([CH2:37][S:38][C:39]3[N:43]([CH2:44][CH:45]=[CH2:46])[N:42]=[N:41][N:40]=3)[CH2:35][S:36][C@H:31]12.C[Si](CC(N)=O)(C)C>C(OCC)(=O)C.O.CN(C)C=O>[CH3:31][N+:32]([CH3:50])=[CH:33][Cl:3].[Cl-:3].[CH:6]1([O:11][N:12]=[C:13]([C:17]2[N:18]=[C:19]([NH:22][C:23](=[O:28])[C:24]([F:27])([F:26])[F:25])[S:20][CH:21]=2)[C:14]([NH:29][CH:30]2[C:50](=[O:51])[N:32]3[C:33]([C:47]([OH:49])=[O:48])=[C:34]([CH2:37][S:38][C:39]4[N:43]([CH2:44][CH:45]=[CH2:46])[N:42]=[N:41][N:40]=4)[CH2:35][S:36][C@H:31]23)=[O:16])[CH2:7][CH2:8][CH2:9][CH2:10]1

Participants

9

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 54035027HCID 54035027, compoundHCID 704326537-amino-3-(1-allyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid

Product 2

HCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 131712610HCID 131712610, compoundYield 195.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent3×

Procedure

The Vilsmeier reagent was prepared from dry dimethylformamide (2.6 g.), phosphorus oxychloride (5.4 g.) and dry ethyl acetate (10.4 ml) by the conventional method. Dry ethyl acetate (100 ml) was added thereto and then 2-cyclopentyloxyimino-2-[2-(2,2,2-trifluoroacetamido)thiazol-4-yl]acetic acid (syn isomer) (10.4 g.) was added thereto at 0° C. The mixture was stirred for 30 minutes at the same temperature. The resulting mixture was added under -10° C. to a stirred solution of 7-amino-3-(1-allyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (9.6 g) and trimethylsilylacetamide (24.8 g) in dry ethyl acetate (192 ml), and the mixture was stirred for 30 minutes at the same temperature. To the reaction mixture was added water. The ethyl acetate layer was separated and extracted with aqueous solution of sodium bicarbonate (pH 7.5). The aqueous layer was washed twice with ethyl acetate and adjusted to pH 2.0 with 10% hydrochloric acid after addition of ethyl acetate and tetrahydrofuran. The organic layer was separated, washed with water, dried over magnesium sulfate, treated with an activated charcoal and concentrated to dryness. The residue was pulverized with diethyl ether and the powder was collected by filtration and washed with diethyl ether to give 7-[2-cyclopentyloxyimino-2-{2-(2,2,2-trifluoroacetamido)thiazol-4-yl}acetamido]-3-(1-allyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer) (18.18 g).

Workup

  1. customat 0° C
  2. stirringthe mixture was stirred for 30 minutes at the same temperature
  3. customThe ethyl acetate layer was separated
  4. extractionextracted with aqueous solution of sodium bicarbonate (pH 7.5)
  5. washThe aqueous layer was washed twice with ethyl acetate
  6. additionafter addition of ethyl acetate and tetrahydrofuran
  7. customThe organic layer was separated
  8. washwashed with water
  9. dry with materialdried over magnesium sulfate
  10. additiontreated with an activated charcoal
  11. concentrationconcentrated to dryness
  12. filtrationthe powder was collected by filtration
  13. washwashed with diethyl ether

Sources & evidence

ORD record
ord-115839bf97494cf18f6d2b0614390c2f
Source dataset
uspto-grants-1981_12
Patent number
US04304770

Reaction notes

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