Diethyl Ether → HCID 70490162, compound

HRID 325406Notes

Reaction equation

HRID 325406 reaction equation
[CH3:1][N:2]1[C:6]([S:7][CH2:8][C:9]2[CH2:10][S:11][C@@H:12]3[CH:19]([NH:20][C:21](=[O:34])[CH:22]([O:31]C=O)[C:23]4[S:27][C:26]([NH:28]C=O)=[N:25][CH:24]=4)[C:18](=[O:35])[N:13]3[C:14]=2[C:15]([OH:17])=[O:16])=[N:5][N:4]=[N:3]1.P(Cl)(Cl)(Cl)=O.C(OCC)C>CO>[CH3:1][N:2]1[C:6]([S:7][CH2:8][C:9]2[CH2:10][S:11][C@@H:12]3[CH:19]([NH:20][C:21](=[O:34])[CH:22]([OH:31])[C:23]4[S:27][C:26]([NH2:28])=[N:25][CH:24]=4)[C:18](=[O:35])[N:13]3[C:14]=2[C:15]([OH:17])=[O:16])=[N:5][N:4]=[N:3]1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 24813Phosphorus oxychlorideHCID 88705011HCID 88705011, compoundHCID 178482023HCID 178482023, compound

Product 1

HCID 70490162HCID 70490162, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a mixture of 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-[2-formyloxy-2-(2-formylamino-1,3-thiazol-5-yl)acetamido]-3-cephem-4-carboxylic acid, which can be represented as 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-[2-formyloxy-2-(2-formylimino-2,3-dihydro-1,3-thiazol-5-yl)acetamido]-3-cephem-4-carboxylic acid, (1.5 g.) in methanol (30 ml.) was added phosphorus oxychloride (1.06 g.) under ice-cooling and stirring, and the mixture was stirred for 1 hour at the same temperature and then further stirred for 4 hours at room temperature. To the reaction mixture was added diethyl ether (150 ml.), and the precipitates were collected by filtration and then dried. Thus obtained pale yellow powder (1.30 g.) was added to water (30 ml.), and the mixture was adjusted to pH 1 to 2 with 10% hydrochloric acid. The resulting solution was treated with an activated charcoal, washed with ethyl acetate and then adjusted to pH 7 with a 5% sodium bicarbonate aqueous solution. The solution was washed with ethyl acetate, adjusted to pH 3 with 10% hydrochloric acid and then filtered. The aqueous solution was absorbed on a HP-20 (neutral resin) column, which was washed with water and then eluted with an aqueous methanol solution. The eluates containing the object compound were collected and then methanol was distilled off under reduced pressure. The remaining aqueous solution was lyophilized to give 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-[2-hydroxy-2-(2-amino-1,3-thiazol-5-yl)acetamido]-3-cephem-4-carboxylic acid, which can be represented as 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-[2-hydroxy-2-(2-imino-2,3-dihydro-1,3-thiazol-5-yl)acetamido]-3-cephem-4-carboxylic acid, (0.63 g.), mp. 130° to 200° C. (dec.).

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred for 1 hour at the same temperature
  3. stirringfurther stirred for 4 hours at room temperature
  4. filtrationthe precipitates were collected by filtration
  5. customdried
  6. additionThus obtained pale yellow powder (1.30 g.) was added to water (30 ml.)
  7. additionThe resulting solution was treated with an activated charcoal
  8. washwashed with ethyl acetate
  9. washThe solution was washed with ethyl acetate
  10. filtrationfiltered
  11. customThe aqueous solution was absorbed on a HP-20 (neutral resin) column, which
  12. washwas washed with water
  13. washeluted with an aqueous methanol solution
  14. additionThe eluates containing the object compound
  15. customwere collected
  16. distillationmethanol was distilled off under reduced pressure

Sources & evidence

ORD record
ord-e43adb60635146f4966ff835c4b0a575
Source dataset
uspto-grants-1984_04
Patent number
US04440766

Reaction notes

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