Phosphorus pentachloride → benzhydryl (6R)-3-(chloromethyl)-7-[[(2Z)-2-methoxyimino-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 1153923

Reaktionsgleichung

Reaktionsgleichung von HRID 1153923
[NH2:1][CH:2]1[C:27](=[O:28])[N:4]2[C:5]([C:11]([O:13][CH:14]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[O:12])=[C:6]([CH2:9][Cl:10])[CH2:7][S:8][C@H:3]12.C[Si](C([Si](C)(C)C)C(N)=O)(C)C.[CH3:41][O:42]/[N:43]=[C:44](/[C:48]1[N:49]=[C:50]([NH:53][C:54]([C:67]2[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=2)([C:61]2[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=2)[C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)[S:51][CH:52]=1)\[C:45](O)=[O:46].P(Cl)(Cl)(Cl)(Cl)Cl>CC#N.C(Cl)Cl.O>[Cl:10][CH2:9][C:6]1[CH2:7][S:8][C@@H:3]2[CH:2]([NH:1][C:45](=[O:46])/[C:44](=[N:43]\[O:42][CH3:41])/[C:48]3[N:49]=[C:50]([NH:53][C:54]([C:61]4[CH:62]=[CH:63][CH:64]=[CH:65][CH:66]=4)([C:67]4[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=4)[C:55]4[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=4)[S:51][CH:52]=3)[C:27](=[O:28])[N:4]2[C:5]=1[C:11]([O:13][CH:14]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)=[O:12]

Komponenten

8

Edukt 4

HCID 24819Phosphorus pentachlorideHCID 5928144(Z)-2-methoxymino-2-(2-(tritylamino)thiazol-4-yl)acetic acidHCID 11708267BistrimethylsilylacetamidHCID 13239626Benzhydryl 7-Amino-3-chloromethyl-3-cephem-4-carboxylate

Produkt 1

HCID 13239631benzhydryl (6R)-3-(chloromethyl)-7-[[(2Z)-2-methoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6342AcetonitrileLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

Benzhydryl 7-amino-3-chloromethyl-3-cephem-4-carboxylate prepared in Preparation No. 4 (2.29 g, 5.52 mmoles) in CH3CN (57 mL) was treated with bis(trimethylsilyl)acetamide (BSA, 4.09 mL, 16.6 mmoles) at room temperature for 50 minutes to give a clear solution. To the solution was added an acid chloride solution, which was prepared from (Z)-2-methoxyimino-2-(2-tritylaminothiazol-4-yl)acetic acid (IV-1) (2.04 g, 4.60 mmoles) and PCl5 (1.15 g, 5.52 mmoles) in methylene chloride (20 mL). The mixture was stirred at room temperature for 30 minutes, poured into cold water (200 mL) and extracted with ethyl acetate (3×100 mL). The combined extracts were washed with aqueous NaCl, dried and evaporated. The residual syrup (4 g) was chromatographed on a silica gel (150 g) column by eluting with 10:1 and 3:1 mixtures of toluene and ethyl acetate successively. The fractions containing the desired compound were combined and evaporated to afford 2.61 g (68%) of VI-1 as an amorphous powder.

Aufarbeitung

  1. customto give a clear solution
  2. extractionextracted with ethyl acetate (3×100 mL)
  3. washThe combined extracts were washed with aqueous NaCl
  4. customdried
  5. customevaporated
  6. customThe residual syrup (4 g) was chromatographed on a silica gel (150 g) column
  7. washby eluting with 10:1 and 3:1 mixtures of toluene and ethyl acetate successively
  8. additionThe fractions containing the desired compound
  9. customevaporated
  10. customto afford 2.61 g (68%) of VI-1 as an amorphous powder

Quellen und Nachweise

ORD-Eintrag
ord-6bdf289397904421a942736b16186ff1
Quelldatensatz
uspto-grants-1984_12
Patentnummer
US04486586

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