Hydrochloric Acid → HCID 88676167, compound

HRID 365225Notes

Reaction equation

HRID 365225 reaction equation
[C:1]([NH:20][C:21]1[S:22][CH:23]=[C:24](/[C:26](=[N:30]/[O:31][CH2:32][C:33]2[N:34]=[C:35]([NH:38][C:39]([C:52]3[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=3)([C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=3)[C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[S:36][CH:37]=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.[CH:64]([O:77][C:78]([C:80]1[N:85]2[C:86](=[O:89])[CH:87]([NH2:88])[C@H:84]2[S:83][CH2:82][C:81]=1[CH2:90][S:91][C:92]1[N:96]([CH3:97])[N:95]=[N:94][N:93]=1)=[O:79])([C:71]1[CH:76]=[CH:75][CH:74]=[CH:73][CH:72]=1)[C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1.Cl>ClCCl.N1C=CC=CC=1>[CH:64]([O:77][C:78]([C:80]1[N:85]2[C:86](=[O:89])[CH:87]([NH:88][C:27](=[O:29])/[C:26](/[C:24]3[N:25]=[C:21]([NH:20][C:1]([C:8]4[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=4)([C:14]4[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=4)[C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)[S:22][CH:23]=3)=[N:30]\[O:31][CH2:32][C:33]3[N:34]=[C:35]([NH:38][C:39]([C:52]4[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=4)([C:40]4[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=4)[C:46]4[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=4)[S:36][CH:37]=3)[C@H:84]2[S:83][CH2:82][C:81]=1[CH2:90][S:91][C:92]1[N:96]([CH3:97])[N:95]=[N:94][N:93]=1)=[O:79])([C:71]1[CH:72]=[CH:73][CH:74]=[CH:75][CH:76]=1)[C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24819Phosphorus pentachlorideHCID 128735187-Amino-3-(1-methyl-5-tetrazolyl)thiomethyl-3-cephem-4-carboxylic acid benzhydryl esterHCID 13578647HCID 13578647, compound

Product 1

HCID 88676167HCID 88676167, compoundYield 63.4%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent4×

Conditions

Temperature
-35 °C

Procedure

In 6 ml of dichloromethane was suspended 500 mg of (Z)-α-(2-tritylamino-4-thiazolyl)-α-[(2-tritylamino-4-thiazolyl)methoxyimino]acetic acid and after cooling the suspension to 3°-4° C. and adding thereto 133 mg of phosphorus pentachloride, the mixture was stirred for 15 minutes at 3°-4° C. On the other hand, 316 mg of 7-amino-3-(1-methyl-5-tetrazolyl)thiomethyl-3-cephem-4-carboxylic acid benzhydryl ester was dissolved in 6 ml of dichloromethane. After cooling the solution to -35° C. and adding 500 mg of pyridine, the foregoing dichloromethane solution containing acid chloride was added dropwise to the solution. Thereafter, the mixture was stirred for 15 minutes at -20° C. to -30° C., 20 ml of ice water was added to the reaction solution, the pH of the solution was adjusted to 1-2 with 1N hydrochloric acid, and the dichloromethane layer thus formed was separated. The dichloromethane layer was washed with water, dried (over anhydrous magnesium sulfate), and concentrated. The residue thus formed was applied to column chromatography and it was eluted with benzene and then with a mixture of benzene and ethyl acetate (5:1) to provide 510 mg of (Z)-7-{α-(2-tritylamino-4-thiazolyl)-α-[(2-tritylamino-4-thiazolyl)methoxyimino]acetamido}-3-[(1-methyl-5-tetrazolyl)thiomethyl]-3-cephem-4-carboxylic acid benzhydryl ester.

Workup

  1. temperatureafter cooling the suspension to 3°-4° C.
  2. additionadding
  3. additionwas added dropwise to the solution
  4. customwas separated
  5. washThe dichloromethane layer was washed with water
  6. dry with materialdried (over anhydrous magnesium sulfate)
  7. concentrationconcentrated
  8. customThe residue thus formed
  9. washwas eluted with benzene
  10. additionwith a mixture of benzene and ethyl acetate (5:1)

Sources & evidence

ORD record
ord-551ef467c05e4b038e0fade54788aa43
Source dataset
uspto-grants-1986_08
Patent number
US04608373

Reaction notes

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