Phosphorus pentachloride → benzhydryl (6R)-3-(chloromethyl)-7-[[(2Z)-2-[1-[(2-methylpropan-2-yl)oxycarbonyl]cyclobutyl]oxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 2164981Notes

Reaction equation

HRID 2164981 reaction equation
P(Cl)(Cl)(Cl)(Cl)Cl.[C:7]([O:11][C:12]([C:14]1([O:18]/[N:19]=[C:20](/[C:24]2[N:25]=[C:26]([NH:29][C:30]([C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[S:27][CH:28]=2)\[C:21]([OH:23])=O)[CH2:17][CH2:16][CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8].Cl.[NH2:50][CH:51]1[C:76](=[O:77])[N:53]2[C:54]([C:60]([O:62][CH:63]([C:70]3[CH:75]=[CH:74][CH:73]=[CH:72][CH:71]=3)[C:64]3[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=3)=[O:61])=[C:55]([CH2:58][Cl:59])[CH2:56][S:57][C@H:52]12>C(Cl)Cl>[C:7]([O:11][C:12]([C:14]1([O:18]/[N:19]=[C:20](/[C:24]2[N:25]=[C:26]([NH:29][C:30]([C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)([C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)[C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[S:27][CH:28]=2)\[C:21]([NH:50][CH:51]2[C:76](=[O:77])[N:53]3[C:54]([C:60]([O:62][CH:63]([C:64]4[CH:65]=[CH:66][CH:67]=[CH:68][CH:69]=4)[C:70]4[CH:75]=[CH:74][CH:73]=[CH:72][CH:71]=4)=[O:61])=[C:55]([CH2:58][Cl:59])[CH2:56][S:57][C@H:52]23)=[O:23])[CH2:15][CH2:16][CH2:17]1)=[O:13])([CH3:10])([CH3:8])[CH3:9]

Participants

5

Reactant 3

HCID 24819Phosphorus pentachlorideHCID 12801754(2Z)-2-[1-[(2-methylpropan-2-yl)oxycarbonyl]cyclobutyl]oxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetic acidHCID 13239629Benzhydryl 7-amino-3-chloromethyl-3-cephem-4-carboxylate hydrochloride

Product 1

HCID 141554130benzhydryl (6R)-3-(chloromethyl)-7-[[(2Z)-2-[1-[(2-methylpropan-2-yl)oxycarbonyl]cyclobutyl]oxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Phosphorus pentachloride (1.46 g, 7 mmoles) was added to a suspension of (Z)-2-(1-t-butoxycarbonylcyclobut-1-oxyimino)-2-(2-tritylaminothiazol-4-yl)acetic acid [IV-5'] (4.09 g, 7 mmoles) in 70 mL of dry methylene chloride, and the mixture was stirred for 1 hour at room temperature. The acid chloride solution was added at -20° C. to a solution of silylated 7-ACA ester, which was prepared by adding BSA (5.6 mL, 21 mmoles) to a stirred suspension of benzhydryl 7-amino-3-chloromethyl-3-cephem-4-carboxylate hydrochloride [V] (3.16 g, 7 mmoles) in dry methylene chloride (70 mL). The mixture was stirred for 20 minutes at -10° C. and then at room temperature for 40 minutes. The reaction mixture was evaporated and diluted with ethyl acetate (300 mL), and the organic layer was washed with 5% aqueous sodium bicarbonate, water and a saturated sodium chloride solution. After drying over sodium sulfate, the solvent was evporated and the residue was purified by silica gel column chromatography (Wako gel C-200, 60 g); elution with chloroform. The fractions containing the desired product were combined and evaporated to obtain 5.88 g (86%) of VI-5' as a yellow powder.

Workup

  1. customwas prepared
  2. additionby adding BSA (5.6 mL, 21 mmoles)
  3. stirringThe mixture was stirred for 20 minutes at -10° C.
  4. waitat room temperature for 40 minutes
  5. customThe reaction mixture was evaporated
  6. additiondiluted with ethyl acetate (300 mL)
  7. washthe organic layer was washed with 5% aqueous sodium bicarbonate, water
  8. dry with materialAfter drying over sodium sulfate
  9. customthe residue was purified by silica gel column chromatography (Wako gel C-200, 60 g)
  10. washelution with chloroform
  11. additionThe fractions containing the desired product
  12. customevaporated
  13. customto obtain 5.88 g (86%) of VI-5' as a yellow powder

Sources & evidence

ORD record
ord-5dda5552895c44ff8f0a1728bcdec0dc
Source dataset
uspto-grants-1985_03
Patent number
US04507487

Reaction notes

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