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

HRID 1153927Notes

Reaction equation

HRID 1153927 reaction equation
P(Cl)(Cl)(Cl)(Cl)Cl.[CH2:7]([O:10]/[N:11]=[C:12](/[C:16]1[N:17]=[C:18]([NH:21][C:22]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[S:19][CH:20]=1)\[C:13]([OH:15])=O)[C:8]#[CH:9].[NH2:41][CH:42]1[C:67](=[O:68])[N:44]2[C:45]([C:51]([O:53][CH:54]([C:61]3[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=3)[C:55]3[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=3)=[O:52])=[C:46]([CH2:49][Cl:50])[CH2:47][S:48][C@H:43]12.C/C(/O[Si](C)(C)C)=N\[Si](C)(C)C.C([O-])(O)=O.[Na+]>ClCCl>[Cl:50][CH2:49][C:46]1[CH2:47][S:48][C@@H:43]2[CH:42]([NH:41][C:13](=[O:15])/[C:12](=[N:11]\[O:10][CH2:7][C:8]#[CH:9])/[C:16]3[N:17]=[C:18]([NH:21][C:22]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[C:35]4[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=4)[S:19][CH:20]=3)[C:67](=[O:68])[N:44]2[C:45]=1[C:51]([O:53][CH:54]([C:61]1[CH:62]=[CH:63][CH:64]=[CH:65][CH:66]=1)[C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1)=[O:52]

Participants

7

Reactant 5

HCID 24819Phosphorus pentachlorideHCID 516892Sodium BicarbonateHCID 6913588N,O-bis(trimethylsilyl)acetamideHCID 13239626Benzhydryl 7-Amino-3-chloromethyl-3-cephem-4-carboxylateHCID 15593555(2Z)-2-prop-2-ynoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetic acid

Product 1

HCID 88600476benzhydryl (6R)-3-(chloromethyl)-8-oxo-7-[[(2Z)-2-prop-2-ynoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Phosphorus pentachloride (910 mg) was added to a solution of (Z)-2-propargyloxyimino-2-(2-tritylaminothiazol-4-yl)acetic acid (IV-7) (1.7 g, 3.6 mmoles) in dichloromethane (30 mL). After stirring for 1 hour at room temperature the mixture was added in one portion to an ice-cooled solution of (V) (1.98 g, 4.4 mmoles) and N,O-bis(trimethylsilyl)acetamide (1.5 mL) in dichloromethane (30 mL). After stirring for 1 hour, the reaction mixture was poured into 10% aqueous NaHCO3 (300 mL) and extracted with ethyl acetate (300 mL). The extract was washed with water, dried over MgSO4 and evaporated under reduced pressure. The residue was chromatographed on a silica gel column. Elution with CHCl3 gave the title compound [VI-7] as an amorphous powder weighing 2.1 g (66%).

Workup

  1. stirringAfter stirring for 1 hour
  2. extractionextracted with ethyl acetate (300 mL)
  3. washThe extract was washed with water
  4. dry with materialdried over MgSO4
  5. customevaporated under reduced pressure
  6. customThe residue was chromatographed on a silica gel column
  7. washElution with CHCl3

Sources & evidence

ORD record
ord-da423bfacc224f508d28f8648fe2872a
Source dataset
uspto-grants-1984_12
Patent number
US04486586

Reaction notes

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