Phosphorus oxychloride → Chloro-N,N-dimethylformiminium chloride

HRID 648416Notes

Reaction equation

HRID 648416 reaction equation
P(Cl)(Cl)([Cl:3])=O.[C:6]([O:25][N:26]=[C:27]([C:31]1[N:32]=[C:33]([NH:36][C:37]([C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[S:34][CH:35]=1)[C:28]([OH:30])=O)([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[NH2:56][CH:57]1[C:78](=[O:79])[N:59]2[C:60]([C:75]([OH:77])=[O:76])=[C:61]([CH2:64][S:65][C:66]3[N:70]([CH2:71][C:72]([OH:74])=[O:73])[N:69]=[N:68][N:67]=3)[CH2:62][S:63][C@H:58]12.C[Si](CC(N)=O)(C)C.C[Si](C([Si](C)(C)C)C(N)=O)(C)C>O.C(OCC)(=O)C.C(Cl)Cl.CN(C)C=O>[CH3:58][N+:59]([CH3:78])=[CH:60][Cl:3].[Cl-:3].[C:6]([O:25][N:26]=[C:27]([C:31]1[N:32]=[C:33]([NH:36][C:37]([C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)([C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)[C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=2)[S:34][CH:35]=1)[C:28]([NH:56][CH:57]1[C:78](=[O:79])[N:59]2[C:60]([C:75]([OH:77])=[O:76])=[C:61]([CH2:64][S:65][C:66]3[N:70]([CH2:71][C:72]([OH:74])=[O:73])[N:69]=[N:68][N:67]=3)[CH2:62][S:63][C@H:58]12)=[O:30])([C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

11

Reactant 5

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 11708267BistrimethylsilylacetamidHCID 127691497-amino-3-(1-carboxymethyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acidHCID 53447342HCID 53447342, compound

Product 2

HCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 1317124087-[2-trityloxyimino-2-(2-tritylamino-1,3-thiazol-4-yl)acetamido]-3-(1-carboxymethyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
-3 °C

Procedure

The Vilsmeier reagent was prepared from dry dimethylformamide (0.26 ml), phosphorus oxychloride (0.31 ml) and dry ethyl acetate (1 ml) according to a conventional method. Dry methylene chloride (40 ml) and 2-trityloxyimino-2-(2-tritylamino-1,3-thiazol-4-yl)acetic acid (syn isomer) (2.1 g) were added thereto at -3° C., and the resulting mixture was stirred for 30 minuts at the same temperature. The resulting solution was added at -10° C. to a suspension, which was prepared by stirring and warming at 40° C. a mixture of 7-amino-3-(1-carboxymethyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (1.0 g), dry ethyl acetate (40 ml), trimethylsilylacetamide (2.9 g) and bis(trimethylsilyl)acetamide (1.7 g), and the resulting mixture was stirred for 2 hours at -10° to -5° C. Water (30 ml) was added to the reaction mixture and the mixture was filtered. To the filtrate was added methylene chloride (20 ml) and the organic layer was separated. To the organic layer was added water (30 ml) and the mixture was adjusted to pH 7.0 with sodium bicarbonate. The aqueous layer was separated, washed with ethyl acetate and, after addition of ethyl acetate (100 ml), adjusted to pH 3.0 under stirring with conc. hydrochloric acid. The ethyl acetate layer was separated, washed with water, dried over magnesium sulfate and concentrated to dryness to give 7-[2-trityloxyimino-2-(2-tritylamino-1,3-thiazol-4-yl)acetamido]-3-(1-carboxymethyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer) (0.48 g).

Workup

  1. additionThe resulting solution was added at -10° C. to a suspension, which
  2. customwas prepared
  3. stirringby stirring
  4. temperaturewarming at 40° C.
  5. stirringthe resulting mixture was stirred for 2 hours at -10° to -5° C
  6. filtrationthe mixture was filtered
  7. additionTo the filtrate was added methylene chloride (20 ml)
  8. customthe organic layer was separated
  9. additionTo the organic layer was added water (30 ml)
  10. customThe aqueous layer was separated
  11. washwashed with ethyl acetate
  12. additionafter addition of ethyl acetate (100 ml)
  13. stirringunder stirring with conc. hydrochloric acid
  14. customThe ethyl acetate layer was separated
  15. washwashed with water
  16. dry with materialdried over magnesium sulfate
  17. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-85481b81f12441759be3cc2a6b1d7688
Source dataset
uspto-grants-1983_10
Patent number
US04411898

Reaction notes

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