Dicyclohexylcarbodiimide → benzhydryl 7-[2-(2-tritylaminothiazol-4-yl)-3-hydroxypropionamido]-3-[(Z)-2-(3-pyridyl)vinylthio]-3-cephem-4-carboxylate

HRID 2351146Notes

Reaction equation

HRID 2351146 reaction equation
[NH2:1][CH:2]1[C:34](=[O:35])[N:4]2[C:5]([C:18]([O:20][CH:21]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[O:19])=[C:6]([S:9]/[CH:10]=[CH:11]\[C:12]3[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=3)[CH2:7][S:8][C@H:3]12.[C:36]([NH:55][C:56]1[S:57][CH:58]=[C:59]([CH:61]([CH2:65][OH:66])[C:62](O)=[O:63])[N:60]=1)([C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)([C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.C1(N=C=NC2CCCCC2)CCCCC1>O1CCCC1>[C:36]([NH:55][C:56]1[S:57][CH:58]=[C:59]([CH:61]([CH2:65][OH:66])[C:62]([NH:1][CH:2]2[C:34](=[O:35])[N:4]3[C:5]([C:18]([O:20][CH:21]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)[C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)=[O:19])=[C:6]([S:9]/[CH:10]=[CH:11]\[C:12]4[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=4)[CH2:7][S:8][C@H:3]23)=[O:63])[N:60]=1)([C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)([C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1

Participants

5

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 136050753-Hydroxy-2-(2-tritylaminothiazol-4-yl)propionic acidHCID 67948113benzhydryl 7-amino-3-[(Z)-2-(3-pyridyl)vinylthio]-3-cephem-4-carboxylate

Product 1

HCID 131716160benzhydryl 7-[2-(2-tritylaminothiazol-4-yl)-3-hydroxypropionamido]-3-[(Z)-2-(3-pyridyl)vinylthio]-3-cephem-4-carboxylateYield 40.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of benzhydryl 7-amino-3-[(Z)-2-(3-pyridyl)vinylthio]-3-cephem-4-carboxylate (1.50 g) and 2-(2-tritylaminothiazol-4-yl)-3-hydroxypropionic acid (1.42 g) in tetrahydrofuran was added N,N'-dicyclohexyl-carbodiimide (925 mg) under ice-cooling. The resultant mixture was stirred for 1 hour at the same temperature and stirred for 2 hours at ambient temperature. The resultant precipitate was filtered off. To the filtrate was added ethyl acetate (100 ml) and the organic layer was separated, washed with a saturated aqueous solution of sodium chloride (50 ml) and dried over magnesium sulfate. The solvent was distilled off and the residue was subjected to column chromatography on silica gel (120 g) and eluted with a mixture of ethyl acetate and diisopropyl ether (3:1). The fractions containing the object compound were combined and concentrated in vacuo to give benzhydryl 7-[2-(2-tritylaminothiazol-4-yl)-3-hydroxypropionamido]-3-[(Z)-2-(3-pyridyl)vinylthio]-3-cephem-4-carboxylate (1.10 g).

Workup

  1. temperaturecooling
  2. filtrationThe resultant precipitate was filtered off
  3. additionTo the filtrate was added ethyl acetate (100 ml)
  4. customthe organic layer was separated
  5. washwashed with a saturated aqueous solution of sodium chloride (50 ml)
  6. dry with materialdried over magnesium sulfate
  7. distillationThe solvent was distilled off
  8. washeluted with a mixture of ethyl acetate and diisopropyl ether (3:1)
  9. additionThe fractions containing the object compound
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ae08109f104a4c08ba0905b1d472c43c
Source dataset
uspto-grants-1989_10
Patent number
US04871730

Reaction notes

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