Water → HCID 88403825, compound

HRID 728582Notes

Reaction equation

HRID 728582 reaction equation
[N:1]([CH2:4][C:5]1[CH2:6][S:7][C@@H:8]2[CH:15]([NH:16][C:17](=[O:56])/[C:18](/[C:31]3[N:32]=[C:33]([NH:36]C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[S:34][CH:35]=3)=[N:19]\[O:20][C:21]([C:24]([O:26]C(C)(C)C)=[O:25])([CH3:23])[CH3:22])[C:14](=[O:57])[N:9]2[C:10]=1[C:11]([OH:13])=[O:12])=[N+]=[N-].O>[Ni].CO.C(O)(C(F)(F)F)=O>[NH2:1][CH2:4][C:5]1[CH2:6][S:7][C@@H:8]2[CH:15]([NH:16][C:17](=[O:56])/[C:18](/[C:31]3[N:32]=[C:33]([NH2:36])[S:34][CH:35]=3)=[N:19]\[O:20][C:21]([C:24]([OH:26])=[O:25])([CH3:23])[CH3:22])[C:14](=[O:57])[N:9]2[C:10]=1[C:11]([OH:13])=[O:12]

Participants

6

Reactant 2

HCID 962WaterHCID 145805801HCID 145805801, compound

Product 1

HCID 88403825HCID 88403825, compoundYield 35.1%

Reagents, catalysts & solvents 3

HCID 935NickelCatalystHCID 887MethanolSolventHCID 6422Trifluoroacetic acidSolvent2×

Procedure

An aqueous slurry of Raney nickel (10.2 g.) was added in one portion to a stirred solution of the azide (20.0 g.) in a mixture of MeOH (60 ml.) and TFA (60 ml.) at room temperature. A vigorous effervescence was observed. Stirring was continued for 1 hour and the Raney nickel was removed by filtration through diatomaceous earth. The filter pad was washed well with MeOH and the washings were combined with the filtrate. The solvents were evaporated under reduced pressure to give a pale green solid residue which was then stirred for 2 hours with a mixture of TFA (60 ml.) and water (15ml.). This mixture was evaporated to dryness and the residue was stirred vigorously with water (400 ml.) for 30 minutes. The resulting solution was filtered through diatomaceous earth to remove the undissolved triphenylmethanol and the filtrate was applied to a column of Diaion HP 20 resin (1 1.). The column was eluted with water (500 ml.) to remove inorganic material and then with aqueous MeOH 1:1 v/v. The fractions which were shown by HPLC to contain the product were evaporated under reduced pressure to yield 3-aminomethyl-7-[2-(2-aminothiazol-4-yl)-2-((Z)-1-carboxy-1-methylethoxyimino)acetamido]ceph-3-em-4-carboxylic acid (4.2 g.) as a pale yellow foam having the following n.m.r. in solvent A: 1.4 (s,6H); 3.1-3.8 (complex, 4H); 4.95 (d,1H); 5.7(d,1H); 6.72 (s,1H).

Workup

  1. customthe Raney nickel was removed by filtration through diatomaceous earth
  2. washThe filter pad was washed well with MeOH
  3. customThe solvents were evaporated under reduced pressure
  4. customto give a pale green solid residue which
  5. customThis mixture was evaporated to dryness
  6. stirringthe residue was stirred vigorously with water (400 ml.) for 30 minutes
  7. filtrationThe resulting solution was filtered through diatomaceous earth
  8. customto remove the undissolved triphenylmethanol
  9. washThe column was eluted with water (500 ml.)
  10. customto remove inorganic material
  11. customwere evaporated under reduced pressure

Sources & evidence

ORD record
ord-4d42e45291e349e0b6fa1795e4e87b8c
Source dataset
uspto-grants-1991_09
Patent number
US05049558

Reaction notes

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