Hydrochloric Acid → 2-Benzhydryloxycarbonyl-7-[2-(2-t-butoxycarbonylprop-2-yl-oxyimino)-2-(2-tritylaminothiazol-4-yl)-acetamido]-8-oxo-3-[2-(pyridin-3-yl-amino)-thiazol-5-yl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene

HRID 1583872Notes

Reaction equation

HRID 1583872 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([NH:7][C:8]([NH2:10])=[S:9])[CH:2]=1.[CH:11]([O:24][C:25]([C:27]1[N:28]2[CH:31]([S:32][CH2:33][C:34]=1[CH:35](Br)[CH:36]=O)[CH:30]([NH:39][C:40](=[O:79])[C:41](=[N:67][O:68][C:69]([C:72]([O:74][C:75]([CH3:78])([CH3:77])[CH3:76])=[O:73])([CH3:71])[CH3:70])[C:42]1[N:43]=[C:44]([NH:47][C:48]([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)[C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)[S:45][CH:46]=1)[C:29]2=[O:80])=[O:26])([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.N1C=CC=CC=1.Cl>O1CCCC1.C(OCC)(=O)C.O>[CH:11]([O:24][C:25]([C:27]1[N:28]2[CH:31]([S:32][CH2:33][C:34]=1[C:35]1[S:9][C:8]([NH:7][C:3]3[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=3)=[N:10][CH:36]=1)[CH:30]([NH:39][C:40](=[O:79])[C:41](=[N:67][O:68][C:69]([C:72]([O:74][C:75]([CH3:78])([CH3:77])[CH3:76])=[O:73])([CH3:70])[CH3:71])[C:42]1[N:43]=[C:44]([NH:47][C:48]([C:55]3[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=3)([C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)[C:61]3[CH:62]=[CH:63][CH:64]=[CH:65][CH:66]=3)[S:45][CH:46]=1)[C:29]2=[O:80])=[O:26])([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 27605153-PyridylthioureaHCID 736670952-Benzhydryloxycarbonyl-3-(1-bromo-2-oxoethyl)-7-[2-(2-t-butoxycarbonylprop-2-yl-oxyimino)-2-(2-tritylaminothiazol-4-yl)-acetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene

Product 1

HCID 538049402-Benzhydryloxycarbonyl-7-[2-(2-t-butoxycarbonylprop-2-yl-oxyimino)-2-(2-tritylaminothiazol-4-yl)-acetamido]-8-oxo-3-[2-(pyridin-3-yl-amino)-thiazol-5-yl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of (pyridin-3-yl)-thiourea (0.08 g) and the syn isomer of 2-benzhydryloxycarbonyl-3-(1-bromo-2-oxoethyl)-7-[2-(2-t-butoxycarbonylprop-2-yl-oxyimino)-2-(2-tritylaminothiazol-4-yl)-acetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (mixture of the two diastereoisomers in respect of the substituent in the 3-position) (0.55 g) in tetrahydrofuran (10 cc) is stirred for 35 minutes at 25° C. and then treated with pyridine (0.042 cc) and water (1 cc). The reaction mixture is stirred for 16 hours at 25° C. and then poured into a mixture of ethyl acetate (50 cc) and 0.2 N hydrochloric acid (50 cc). The organic solution is washed with a saturated solution of sodium bicarbonate (50 cc), water (3×50 cc) and then with a saturated solution of sodium chloride (20 cc) and dried over magnesium sulphate. The residue obtained after evaporation of the solvent to dryness under reduced pressure (4 kPa) at 30° C. is chromatographed on a column (height: 24 cm, diameter: 2 cm) containing silica gel (0.04-0.06 mm), elution being carried out under a pressure of 0.5 bar (50 kPa) with a mixture of cyclohexane and ethyl acetate (15/85 by volume) and 15 cc fractions being collected. Fractions 7 to 13 are combined and concentrated to dryness under reduced pressure (4 kPa) at 30° C. to give the syn isomer of 2-benzhydryloxycarbonyl-7-[2-(2-t-butoxycarbonylprop-2-yl-oxyimino)-2-(2-tritylaminothiazol-4-yl)-acetamido]-8-oxo-3-[2-(pyridin-3-yl-amino)-thiazol-5-yl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene (0.39 g) in the form of a hard yellow foam.

Workup

  1. stirringThe reaction mixture is stirred for 16 hours at 25° C.
  2. washThe organic solution is washed with a saturated solution of sodium bicarbonate (50 cc), water (3×50 cc)
  3. dry with materialwith a saturated solution of sodium chloride (20 cc) and dried over magnesium sulphate
  4. customThe residue obtained
  5. customafter evaporation of the solvent to dryness under reduced pressure (4 kPa) at 30° C.
  6. customis chromatographed on a column (height: 24 cm, diameter: 2 cm)
  7. additioncontaining
  8. washsilica gel (0.04-0.06 mm), elution
  9. additionbeing carried out under a pressure of 0.5 bar (50 kPa) with a mixture of cyclohexane and ethyl acetate (15/85 by volume) and 15 cc fractions
  10. custombeing collected
  11. concentrationconcentrated to dryness under reduced pressure (4 kPa) at 30° C.

Sources & evidence

ORD record
ord-7f6c680837554905a5443f3c79eaa744
Source dataset
uspto-grants-1985_11
Patent number
US04554350

Reaction notes

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