Hydrochloric Acid → HCID 178491515, compound

HRID 2253985Notes

Reaction equation

HRID 2253985 reaction equation
[C:1]([NH:20][C:21]1[S:22][CH:23]=[C:24](/[C:26](=[N:30]/[O:31][CH:32]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[C:33]2[CH:34]=[N:35][CH:36]=[CH:37][CH:38]=2)/[C:27]([OH:29])=O)[N:25]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P(Cl)(Cl)(Cl)(Cl)Cl.Cl.[NH2:53][CH:54]1[C:75](=[O:76])[N:56]2[C:57]([C:63]([O:65][CH2:66][C:67]3[CH:72]=[CH:71][C:70]([O:73][CH3:74])=[CH:69][CH:68]=3)=[O:64])=[C:58]([CH2:61][Cl:62])[CH2:59][S:60][C@H:55]12.Cl>ClCCl.N1C=CC=CC=1>[C:1]([NH:20][C:21]1[S:22][CH:23]=[C:24](/[C:26](=[N:30]/[O:31][CH:32]([C:39]([O:41][C:42]([CH3:45])([CH3:43])[CH3:44])=[O:40])[C:33]2[CH:34]=[N:35][CH:36]=[CH:37][CH:38]=2)/[C:27]([NH:53][C@@H:54]2[C:75](=[O:76])[N:56]3[C:57]([C:63]([O:65][CH2:66][C:67]4[CH:72]=[CH:71][C:70]([O:73][CH3:74])=[CH:69][CH:68]=4)=[O:64])=[C:58]([CH2:61][Cl:62])[CH2:59][S:60][C@H:55]23)=[O:29])[N:25]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24819Phosphorus pentachlorideHCID 14032025HCID 14032025, compoundHCID 19746636HCID 19746636, compound

Product 1

HCID 178491515HCID 178491515, compoundYield 57.9%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
5 °C

Procedure

After 1.0 g (1.6 mmol) of (Z)-2-(2-tritylaminothiazol-4-yl)-[[(tert-butoxycarbonyl)(3-pyridyl)methoxy]imino]acetic acid and 0.37 g (1.77 mmol) of phosphorus pentachloride were added to 25 ml of dichloromethane, the mixture was stirred at 5° C. for 30 minutes. The resulting solution was dropwise added to a solution containing 0.65 g (1.6 mmol) of p-methoxybenzyl 7-amino-3-chloromethyl-3-cephem-4-carboxylate hydrochloride and 1.3 ml of pyridine in 30 ml of dichloromethane. After stirring for an hour below -20° C., the solution was cooled to -40° C. After adding 50 ml of 1N hydrochloric acid, the temperature was reverted to room temperature. The dichloromethane layer was taken out, washed with saturated sodium chloride aqueous solution and dried over anhydrous magnesium sulfate. The solvent was distilled off and the residue was subjected to silica gel column chromatography. The column was eluted with dichloromethane-methanol (10:1) to give 0.90 g (57.7%) of p-methoxybenzyl 7β-[(Z)-2-(2-tritylamino-4-thiazolyl)-2-[[(R S)-(tert-butoxycarbonyl)(3-pyridyl)methoxy]imino]acetamido]-3-chloromethyl-3-cephem-4-carboxylate.

Workup

  1. additionThe resulting solution was dropwise added to a solution
  2. stirringAfter stirring for an hour below -20° C.
  3. temperaturethe solution was cooled to -40° C
  4. customwas reverted to room temperature
  5. washwashed with saturated sodium chloride aqueous solution
  6. dry with materialdried over anhydrous magnesium sulfate
  7. distillationThe solvent was distilled off
  8. washThe column was eluted with dichloromethane-methanol (10:1)

Sources & evidence

ORD record
ord-afb23ebadf404c8a950e8e2f289a9d5e
Source dataset
uspto-grants-1993_08
Patent number
US05233035

Reaction notes

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