Phosphorus pentachloride → benzhydryl (6R)-3-(chloromethyl)-7-[[(2Z)-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]imino-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 615788Notes

Reaction equation

HRID 615788 reaction equation
[C:1]([O:5][C:6]([CH2:8][O:9]/[N:10]=[C:11](/[C:15]1[N:16]=[C:17]([NH:20][C:21]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[S:18][CH:19]=1)\[C:12](O)=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].P(Cl)(Cl)(Cl)(Cl)Cl.C[Si](C([Si](C)(C)C)C(N)=O)(C)C.Cl.[NH2:59][CH:60]1[C:85](=[O:86])[N:62]2[C:63]([C:69]([O:71][CH:72]([C:79]3[CH:84]=[CH:83][CH:82]=[CH:81][CH:80]=3)[C:73]3[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=3)=[O:70])=[C:64]([CH2:67][Cl:68])[CH2:65][S:66][C@H:61]12>C(Cl)Cl.C(OCC)(=O)C>[C:1]([O:5][C:6]([CH2:8][O:9]/[N:10]=[C:11](/[C:15]1[N:16]=[C:17]([NH:20][C:21]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)([C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[S:18][CH:19]=1)\[C:12]([NH:59][CH:60]1[C:85](=[O:86])[N:62]2[C:63]([C:69]([O:71][CH:72]([C:73]3[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=3)[C:79]3[CH:80]=[CH:81][CH:82]=[CH:83][CH:84]=3)=[O:70])=[C:64]([CH2:67][Cl:68])[CH2:65][S:66][C@H:61]12)=[O:13])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 24819Phosphorus pentachlorideHCID 11708267BistrimethylsilylacetamidHCID 13078701(2Z)-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]imino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetic acidHCID 13239629Benzhydryl 7-amino-3-chloromethyl-3-cephem-4-carboxylate hydrochloride

Product 1

HCID 87882460benzhydryl (6R)-3-(chloromethyl)-7-[[(2Z)-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]imino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateYield 67%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To an ice-cooled solution of (Z)-2-t-butoxycarbonylmethoxyimino-2-(tritylaminothiazol-4-yl)acetic acid (IVg') (2.71 g, 5 mmoles) in CH2Cl2 (20 ml) was added PCl5 (1.24 g, 6 mmoles), and the solution was stirred for 20 minutes at room temperature. The acid chloride solution was added under ice-cooling to a solution of the silylated 7-ACA ester, which was prepared by adding bis(trimethylsilyl)acetamide (BSA, 3.7 ml, 15 mmoles) to a stirred suspension of benzhydryl 7-amino-3-chloromethyl-3-cephem-4-carboxylate hydrochloride (V) (2.25 g, 5 mmoles) in CH2Cl2 (20 ml). The reaction mixture was stirred at room temperature for 30 minutes, diluted with ethyl acetate (200 ml) and washed with an aqueous NaHCO3 solution and water. After drying over Na2SO4, the solution was evaporated and the residue was purified by silica gel chromatography (Wako gel C-200, 60 g). The desired fractions, eluted by CHCl3, were combined and concentrated to give 3.16 g (67%) of the title compound VIg'.

Workup

  1. customwas prepared
  2. stirringThe reaction mixture was stirred at room temperature for 30 minutes
  3. washwashed with an aqueous NaHCO3 solution and water
  4. dry with materialAfter drying over Na2SO4
  5. customthe solution was evaporated
  6. customthe residue was purified by silica gel chromatography (Wako gel C-200, 60 g)
  7. washThe desired fractions, eluted by CHCl3
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-800dadbfc4c644ffaa50a81b9f94575e
Source dataset
uspto-grants-1985_02
Patent number
US04500526

Reaction notes

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