Toluene → HCID 57255092, compound

HRID 1252641Notes

Reaction equation

HRID 1252641 reaction equation
FC(F)(F)C(O)=O.CC(C)C(OC(C1C=CC=CC=1)C1C=CC=CC=1)=O.C1(C)C=CC=CC=1.[NH2:34][C:35]1[S:36][CH:37]=[C:38]([C:40](=[N:65][O:66][C:67]([CH3:85])([CH3:84])[C:68]([O:70]C(C2C=CC=CC=2)C2C=CC=CC=2)=[O:69])[C:41]([NH:43][C@H:44]2[CH2:47][N:46]([C:48]([NH:50][S:51]([NH:54][CH2:55][C:56]3[NH:57][CH:58]=[C:59]([OH:63])[C:60](=[O:62])[CH:61]=3)(=[O:53])=[O:52])=[O:49])[C:45]2=[O:64])=[O:42])[N:39]=1>ClCCl.C1(OC)C=CC=CC=1.CC#N.O>[NH2:34][C:35]1[S:36][CH:37]=[C:38]([C:40](=[N:65][O:66][C:67]([CH3:85])([CH3:84])[C:68]([OH:70])=[O:69])[C:41]([NH:43][C@H:44]2[CH2:47][N:46]([C:48]([NH:50][S:51]([NH:54][CH2:55][C:56]3[NH:57][CH:58]=[C:59]([OH:63])[C:60](=[O:62])[CH:61]=3)(=[O:53])=[O:52])=[O:49])[C:45]2=[O:64])=[O:42])[N:39]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 6422Trifluoroacetic acidHCID 17821543HCID 17821543, compoundHCID 86742174HCID 86742174, compound

Product 1

HCID 57255092HCID 57255092, compoundYield 105.8%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 7519AnisoleSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
5 °C

Procedure

Trifluoroacetic acid (4.7 ml) was added dropwise to a stirred suspension of (3S)-2-[[1(2-amino-4-thiazolyl)-2-[[1-[[[[[(1,4-dihydro-5-hydroxy-4-oxo-2-pyridinyl)methyl]amino]sulfonyl]amino]carbonyl]-2-oxo-3-azetidinyl]amino]-2-oxoethylidene]amino]oxy]-2-methylpropanoic acid, diphenylmethyl ester (131 mg, 0.113 mmole) in 3 ml of dichloromethane and 0.3 ml anisole at 0° C. After stirring 45 minutes at 5° C., 2 ml of toluene was added and the volatiles were removed in vacuo. The resulting oil was washed with hexane (3×4 ml) and triturated to a solid with 10 ml of ether. The solid was washed once with ether (10 ml) and dried in vacuo. The above reaction and work-up were repeated on 0.166 mmole of (3S)-2-[[[1-(2-amino-4-thiazolyl)-2-[[1-[[[[[(1,4-dihydro-5-hydroxy-4-oxo-2-pyridinyl)methyl]amino]sulfonyl]amino]carbonyl] -2-oxo-3-azetidinyl]amino]-2-oxoethylidene]amino]oxy]-2-methylpropanoic acid, diphenylmethyl ester. The crude solids were combined, dissolved in 2 ml of acetonitrile-water (40-60) (pH 2.5) and chromatographed on a column (200 ml) of macroreticular styrene-divinylbenzene copolymer, using an acetonitrile-water gradient. The desired material eluted at acetonitrile-water (20-80). The relevant fractions were combined and lyophilized to afford 103 mg of the title compound as a white solid, melting point 180° C., dec.

Workup

  1. customthe volatiles were removed in vacuo
  2. washThe resulting oil was washed with hexane (3×4 ml)
  3. customtriturated to a solid with 10 ml of ether
  4. washThe solid was washed once with ether (10 ml)
  5. customdried in vacuo
  6. customThe above reaction
  7. customchromatographed on a column (200 ml) of macroreticular styrene-divinylbenzene copolymer
  8. washThe desired material eluted at acetonitrile-water (20-80)

Sources & evidence

ORD record
ord-bc33af6cff01461597cdc3451187097e
Source dataset
uspto-grants-1988_05
Patent number
US04743685

Reaction notes

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