Hydrochloric Acid → HCID 178491514, compound

HRID 2253988Notes

Reaction equation

HRID 2253988 reaction equation
[C:1]([NH:20][C:21]1[S:22][CH:23]=[C:24](/[C:26](=[N:30]/[O:31][CH:32]([C:38]([O:40][CH:41]([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)=[O:39])[C:33]2[CH:37]=[CH:36][S:35][CH:34]=2)/[C:27](O)=[O:28])[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.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.[NH2:68][CH:69]1[C:90](=[O:91])[N:71]2[C:72]([C:78]([O:80][CH2:81][C:82]3[CH:87]=[CH:86][C:85]([O:88][CH3:89])=[CH:84][CH:83]=3)=[O:79])=[C:73]([CH2:76][Cl:77])[CH2:74][S:75][C@H:70]12.N1C=CC=CC=1.Cl>ClCCl.O>[C:1]([NH:20][C:21]1[S:22][CH:23]=[C:24](/[C:26](=[N:30]/[O:31][CH:32]([C:38]([O:40][CH:41]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)=[O:39])[C:33]2[CH:37]=[CH:36][S:35][CH:34]=2)/[C:27]([NH:68][C@@H:69]2[C:90](=[O:91])[N:71]3[C:72]([C:78]([O:80][CH2:81][C:82]4[CH:87]=[CH:86][C:85]([O:88][CH3:89])=[CH:84][CH:83]=4)=[O:79])=[C:73]([CH2:76][Cl:77])[CH2:74][S:75][C@H:70]23)=[O:28])[N:25]=1)([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 14812Phosphorus oxide (P4O10)HCID 140320224-Methoxybenzyl 7-amino-3-chloromethyl-3-cephem-4-carboxylateHCID 19746691(2Z)-2-(2-benzhydryloxy-2-oxo-1-thiophen-3-ylethoxy)imino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetic acid

Product 1

HCID 178491514HCID 178491514, compoundYield 93.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-40 °C

Procedure

(Z)-2-(2-tritylamino-4-thiazolyl)-2-[(diphenylmethyloxycarbonyl)(3-thienyl)methyl]oxyiminoacetic acid (1.90 g, 2.58 mmol) and phosphorus pentoxide (0.564 g, 2.71 mmol) were added to dichloromethane (11 ml) under ice-cooling, and then the resulting mixture was stirred for 30 min. Thus obtained solution was added at -60° C. to the solution of 4-methoxybenzyl 7-amino-3-chloromethyl-3-cephem-4-carboxylate (1.046 g, 2.58 mmol) and pyridine (1.04 ml, 12.9 mmol) in dichloromethane (30 ml) at -40° C. The reaction solution was allowed to -20° C. over 40 min. The reaction solution was cooled to -40° C., and 1N hydrochloric acid (12.9 ml) was added thereto. Water was added to the reaction solution, the solution was extracted with dichloromethane (×3), the organic layer was washed with a saturated saline and dried over anhydrous magnesium sulfate, and then the solvent was evaporated to give a caramel (3.50 g). The caramel was subjected to silica gel column chromatography eluting with hexane-ethyl acetate to obtain (4-methoxybenzyl) 7β-[(Z)-2-(2-tritylamino-4-thiazolyl)-2-[[(R S)-(diphenylmethyloxycarbonyl)(3-thienyl)methoxy]imino]acetamido]-3-cloromethyl-3-cephem-4-carboxylate (2.62 g).

Workup

  1. temperaturecooling
  2. waitThe reaction solution was allowed to -20° C. over 40 min
  3. extractionthe solution was extracted with dichloromethane (×3)
  4. washthe organic layer was washed with a saturated saline
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was evaporated
  7. customto give a caramel (3.50 g)
  8. washeluting with hexane-ethyl acetate

Sources & evidence

ORD record
ord-84a519518a3147a9987183ba841ff8f0
Source dataset
uspto-grants-1993_08
Patent number
US05233035

Reaction notes

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