Sodium Bicarbonate → HCID 13175942, compound

HRID 2413424Notes

Reaction equation

HRID 2413424 reaction equation
[C:1]1([NH:7][C:8]([NH2:10])=[S:9])[CH:6]=[CH:5][CH:4]=[CH:3][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](Cl)[CH:36]=O)[CH:30]([NH:39][C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[C:29]2=[O:47])=[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.C(=O)(O)[O-].[Na+]>O1CCCC1.C(O)C.C(OCC)(=O)C>[NH:7]([C:8]1[S:9][C:35]([C:34]2[CH2:33][S:32][CH:31]3[N:28]([C:29](=[O:47])[CH:30]3[NH:39][C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[C:27]=2[C:25]([O:24][CH:11]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[O:26])=[CH:36][N:10]=1)[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 676454PhenylthioureaHCID 13175929HCID 13175929, compound

Product 1

HCID 13175942HCID 13175942, compound

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

N-Phenylthiourea (3.34 g) is added to a solution of 2-benzhydryloxycarbonyl-7-t-butoxycarbonylamino-3-(1-chloro-2-oxoethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (a mixture of the epimers of the chloroaldehyde) (10.3 g) in a mixture of tetrahydrofuran (100 cc) and ethanol (40 cc), and the reaction mixture is then heated at the reflux temperature for 135 minutes. It is diluted with ethyl acetate (250 cc) and a half-saturated sodium bicarbonate solution (500 cc). The organic layer is washed with a half-saturated sodium chloride solution (250 cc) and then dried over magnesium sulphate and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C. The residue obtained is chromatographed on a column (height: 30 cm; diameter: 7 cm) of silica gel (0.04-0.06 mm), elution being carried out under a pressure of 0.7 bar (70 kPa) with a 70:30 (by volume) mixture of cyclohexane and ethyl acetate. After 1.5 liters of eluate have been collected, 100 cc fractions are collected and fractions 20 and 21 are combined and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C. The residue is triturated with isopropyl ether (30 cc). 3-(2-Anilino-thiazol-5-yl)-2-benzhydryloxycarbonyl-7-t-butoxycarbonylamino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (2.7 g) is obtained in the form of a yellow solid.

Workup

  1. temperaturethe reaction mixture is then heated at the reflux temperature for 135 minutes
  2. washThe organic layer is washed with a half-saturated sodium chloride solution (250 cc)
  3. dry with materialdried over magnesium sulphate
  4. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C
  5. customThe residue obtained
  6. customis chromatographed on a column (height: 30 cm; diameter: 7 cm) of silica gel (0.04-0.06 mm), elution
  7. additionbeing carried out under a pressure of 0.7 bar (70 kPa) with a 70:30 (by volume) mixture of cyclohexane and ethyl acetate
  8. customAfter 1.5 liters of eluate have been collected
  9. custom100 cc fractions are collected
  10. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C
  11. customThe residue is triturated with isopropyl ether (30 cc)

Sources & evidence

ORD record
ord-ee0395f2d10e4eefbc38ae2931455a53
Source dataset
uspto-grants-1985_01
Patent number
US04496560

Reaction notes

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