Bromotrimethylsilane → HCID 131712383, compound

HRID 2164683Notes

Reaction equation

HRID 2164683 reaction equation
C[Si](C([Si](C)(C)C)C(N)=O)(C)C.C[Si](Br)(C)C.[P:18]([CH2:22][CH2:23][O:24][N:25]=[C:26]([C:50]1[N:51]=[C:52]([NH:55]C=O)[S:53][CH:54]=1)[C:27]([NH:29][CH:30]1[C:48](=[O:49])[N:32]2[C:33]([C:45]([OH:47])=[O:46])=[C:34]([CH2:37][S:38][C:39]3[N:43]([CH3:44])[N:42]=[N:41][N:40]=3)[CH2:35][S:36][C@H:31]12)=[O:28])([OH:21])([OH:20])=[O:19]>C(Cl)Cl>[P:18]([CH2:22][CH2:23][O:24][N:25]=[C:26]([C:50]1[N:51]=[C:52]([NH2:55])[S:53][CH:54]=1)[C:27]([NH:29][CH:30]1[C:48](=[O:49])[N:32]2[C:33]([C:45]([OH:47])=[O:46])=[C:34]([CH2:37][S:38][C:39]3[N:43]([CH3:44])[N:42]=[N:41][N:40]=3)[CH2:35][S:36][C@H:31]12)=[O:28])([OH:21])([OH:20])=[O:19]

Participants

5

Reactant 3

HCID 76113BromotrimethylsilaneHCID 11708267BistrimethylsilylacetamidHCID 131712384HCID 131712384, compound

Product 1

HCID 131712383HCID 131712383, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 7-[2-{2-(O,O-diethylphosphono)ethoxyimino}-2-(2-formamidothiazol-4-yl)acetamido]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer) (6.2 g.) methylene chloride (90 ml.) and bis(trimethylsilyl)acetamide (9.2 g.) was stirred for 30 minutes at room temperature and thereto was added trimethylsilyl bromide (6.9 g.) over a period of 30 minutes with stirring at 20° to 25° C. and then stirring was continued for 5 hours at 25° to 27° C. The reaction mixture containing 7-[2-(2-phosphonoethoxyimino)-2-(2-formamidothiazol-4-yl)acetamido]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer) was concentrated and to the residue were added cold methanol (100 ml.) and cold conc. hydrochloric acid (4 ml.) followed by stirring for an hour at room temperature and a further addition of conc. hydrochloric acid (2 ml.). The resulting mixture was stirred for an hour at room temperature and then concentrated. To the residue was added water (300 ml.) and the mixture was adjusted to pH 2 to 3 with sodium bicarbonate and then subjected to column chromatography (non-ion adsorption resin, Diaion HP 20 prepared by Mitsubishi Chemical Industries) (200 ml.). The column was washed with water (1 l.) and then eluted successively with 10% methanol (1 l.), 20% methanol (1 l.), 30% methanol (1 l.) and 40% methanol (2 l.). The fractions containing the desired compound were evaporated to give the title compound (3.7 g.), mp. 180° to 210° C. (dec.)

Workup

  1. stirringwith stirring at 20° to 25° C.
  2. stirringstirring
  3. waitwas continued for 5 hours at 25° to 27° C
  4. concentrationwas concentrated and to the residue
  5. additionwere added cold methanol (100 ml.) and cold conc. hydrochloric acid (4 ml.)
  6. stirringby stirring for an hour at room temperature
  7. additiona further addition of conc. hydrochloric acid (2 ml.)
  8. stirringThe resulting mixture was stirred for an hour at room temperature
  9. concentrationconcentrated
  10. additionTo the residue was added water (300 ml.)
  11. customsubjected to column chromatography (non-ion adsorption resin, Diaion HP 20 prepared by Mitsubishi Chemical Industries) (200 ml.)
  12. washThe column was washed with water (1 l.)
  13. washeluted successively with 10% methanol (1 l.), 20% methanol (1 l.), 30% methanol (1 l.) and 40% methanol (2 l.)
  14. additionThe fractions containing the desired compound
  15. customwere evaporated

Sources & evidence

ORD record
ord-7b5bed01e2f04b90a872a8d682a24e94
Source dataset
uspto-grants-1985_03
Patent number
US04506076

Reaction notes

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