Ammonia → (6R)-7-amino-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

HRID 638676Notes

Reaction equation

HRID 638676 reaction equation
ClCC([NH:5][CH:6]1[C:17](=[O:18])[N:8]2[C:9]([C:14]([OH:16])=[O:15])=[C:10]([CH3:13])[CH2:11][S:12][C@H:7]12)=O.C[Si](C)(C)Cl.N.C(N(CCCCCCCCCCCCCCCC)C1C=CC=CC=1)C.P(Cl)(Cl)(Cl)(Cl)Cl>CO.C(Cl)Cl>[NH2:5][CH:6]1[C:17](=[O:18])[N:8]2[C:9]([C:14]([OH:16])=[O:15])=[C:10]([CH3:13])[CH2:11][S:12][C@H:7]12

Participants

8

Reactant 5

HCID 222AmmoniaHCID 6397ChlorotrimethylsilaneHCID 24819Phosphorus pentachlorideHCID 23053402N-ethyl-N-hexadecylanilineHCID 704447617-Chloracetamido-3-methylceph-3-em-4-carboxylic acid

Product 1

HCID 13475828(6R)-7-amino-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acidYield 91.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

8.7 g of 7-chloroacetylamino-3-methyl-3-cephem-4-carboxylic acid are suspended in a 100 ml of methylene dichloride and 7.4 ml of trimethylchlorosilane are added. Dry ammonia gas is then introduced until the temperature which has arisen begins to sink. After refluxing for a short time and cooling to -14°, 15.8 ml of N-ethyl-N-hexadecylaniline are added. 8 g of phosphorus pentachloride are then added in 3 portions so that the temperature does not rise above -10°. The reaction mixture is stirred for a further 30 minutes at -12° to -10° and then poured into 150 ml of methanol, pre-cooled to -14°. The mixture is then mixed with 150 ml of ice water. After strong stirring for a short time, the phases are separated. The aqueous phase is washed with methylene dichloride and the pH is adjusted to 3.8 with ammonia solution. The colourless precipitate is filtered off, washed each time with 30 ml of water and acetone and dried in vacuo at 50°. The title compound (5.85 g; 91%) results as a colourless powder in pure form. The N-ethyl-N-hexadecylaniline base can be regenerated in the same manner as described in Example 1 for N-methyl-N-dodecylaniline.

Workup

  1. additionare added
  2. temperatureAfter refluxing for a short time
  3. temperaturecooling to -14°
  4. customdoes not rise above -10°
  5. temperaturepre-cooled to -14°
  6. stirringAfter strong stirring for a short time
  7. customthe phases are separated
  8. washThe aqueous phase is washed with methylene dichloride
  9. filtrationThe colourless precipitate is filtered off
  10. washwashed each time with 30 ml of water and acetone
  11. customdried in vacuo at 50°

Sources & evidence

ORD record
ord-4d79846158774ca2869d27ae49f7407b
Source dataset
uspto-grants-1985_12
Patent number
US04562253

Reaction notes

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