Hydrochloric Acid → (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-8-oxo-3-[(5-oxo-2H-furan-3-yl)sulfanylmethyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

HRID 467371Notes

Reaction equation

HRID 467371 reaction equation
[O:1]=[C:2]1[CH:6]=[C:5]([S:7][CH2:8][C:9]2[CH2:10][S:11][C@@H:12]3[C@H:32]([NH:33][C:34](=[O:82])/[C:35](/[C:57]4[N:58]=[C:59]([NH:62]C(C5C=CC=CC=5)(C5C=CC=CC=5)C5C=CC=CC=5)[S:60][CH:61]=4)=[N:36]\[O:37]C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[C:31](=[O:83])[N:13]3[C:14]=2[C:15]([O:17]C(C2C=CC=CC=2)C2C=CC=CC=2)=[O:16])[CH2:4][O:3]1.Cl.O>C(O)=O>[NH2:62][C:59]1[S:60][CH:61]=[C:57](/[C:35](=[N:36]/[OH:37])/[C:34]([NH:33][C@@H:32]2[C:31](=[O:83])[N:13]3[C:14]([C:15]([OH:17])=[O:16])=[C:9]([CH2:8][S:7][C:5]4[CH2:4][O:3][C:2](=[O:1])[CH:6]=4)[CH2:10][S:11][C@H:12]23)=[O:82])[N:58]=1

Participants

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 962WaterHCID 141558982benzhydryl (6R,7R)-8-oxo-3-[(5-oxo-2H-furan-3-yl)sulfanylmethyl]-7-[[(2Z)-2-[2-(tritylamino)-1,3-thiazol-4-yl]-2-trityloxyiminoacetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Product 1

HCID 88501503(6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-8-oxo-3-[(5-oxo-2H-furan-3-yl)sulfanylmethyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acidYield 39.7%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Procedure

Diphenylmethyl 3-(2,5-dihydro-2-oxofuran-4-ylthiomethyl)-7β-[2-(2-tritylaminothiazol-4-yl)-2-(Z)-trityloxyiminoacetamido]ceph-3-em-4-carboxylate (744 mg) was dissolved in 98-100% formic acid (13 ml) and 1N hydrochloric acid (0.65 ml) and water (0.65 ml) were added. The mixture was stirred at room temperature for 30 mins and then concentrated hydrochloric acid (0.52 ml) was added. After stirring for a further hour the solvents were removed on a rotary evaporator. A mixture of toluene and tetrahydrofuran was evaporated from the residue twice, and the residue triturated with ether. The solid was filtered off, and washed with ether. The solid was suspended in water and the pH adjusted to 2.6 with 0.1N sodium hydroxide, the mixture was stirred for a further 30 mins, occasionally adjusting the pH to 2.6. The solid was then filtered off, washed with cold water and dried under vacuum to give the title compound (128 mg) as an off-white solid. υmax (KBr) 1773, 1735, 1670, and 1629cm-1. δH [(CD3)2SO] 3.49 (1H, d, J 18.0Hz), 3.72 (1H, d, J 18.1Hz), 4.10 (1H, d, J 13.2Hz), 4.18 (1H, d, J 13.2Hz), 4.97 (2H, s), 5.18 (1H, d, J 4.8Hz), 5.79 (1H, dd, J 4.8 and 8.0Hz), 6.11 (1H, s), 6.67 (1H, s), 9.51 (1H, d, J 8.1Hz), 11.40 (1H, s). [mass spectrum: +ve ion (thioglycerol) MH+ 498].

Workup

  1. stirringAfter stirring for a further hour the solvents
  2. customwere removed on a rotary evaporator
  3. additionA mixture of toluene and tetrahydrofuran
  4. customwas evaporated from the residue twice
  5. customthe residue triturated with ether
  6. filtrationThe solid was filtered off
  7. washwashed with ether
  8. stirringthe mixture was stirred for a further 30 mins
  9. filtrationThe solid was then filtered off
  10. washwashed with cold water
  11. customdried under vacuum

Sources & evidence

ORD record
ord-8f343f9f13d44bc782027e0b918f7261
Source dataset
uspto-grants-1992_10
Patent number
US05158946

Reaction notes

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