Ethyl Acetate → HCID 13319619, compound

HRID 2413433Notes

Reaction equation

HRID 2413433 reaction equation
[CH3:1][N:2]([CH3:9])[CH2:3][CH2:4][NH:5][C:6]([NH2:8])=[S:7].[CH:10]([O:23][C:24]([C:26]1[N:27]2[CH:30]([S:31][CH2:32][C:33]=1[CH:34](Br)[CH:35]=O)[CH:29]([NH:38][C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[C:28]2=[O:46])=[O:25])([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C(OCC)(=O)C.C(=O)(O)[O-].[Na+]>C(Cl)Cl.O1CCCC1.C(#N)C>[CH:10]([O:23][C:24]([C:26]1[N:27]2[CH:30]([S:31][CH2:32][C:33]=1[C:34]1[S:7][C:6]([NH:5][CH2:4][CH2:3][N:2]([CH3:9])[CH3:1])=[N:8][CH:35]=1)[CH:29]([NH:38][C:39]([O:41][C:42]([CH3:44])([CH3:43])[CH3:45])=[O:40])[C:28]2=[O:46])=[O:25])([C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 81871686114-63-8HCID 13175928HCID 13175928, compound

Product 1

HCID 13319619HCID 13319619, compoundYield 3.2%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of 1-(2-dimethylaminoethyl)-thiourea (22 g) in methylene chloride (200 cc) is added to a solution of 2-benzhydryloxycarbonyl-3-(1-bromo-2-oxoethyl)-7-t-butoxycarbonylamino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (88 g) in anhydrous tetrahydrofuran (500 cc). After having been stirred for 24 hours at 25° C., the reaction mixture is poured onto a mixture of ethyl acetate (1.5 liters) and saturated sodium bicarbonate solution (1.5 liters). The organic phase is washed with saturated sodium bicarbonate solution (1 liter), distilled water (1 liter) and saturated sodium chloride solution (1 liter) and is then dried over anhydrous magnesium sulphate. After filtration, and concentration of the filtrate under reduced pressure (20 mm Hg; 2.7 kPa), the residue is purified by chromatography on silica gel (0.063-0.2 mm) [height of the silica layer: 38 cm, column diameter: 10 cm], elution being carried out with methylene chloride (5 liters) and then with a mixture (11 liters) of methylene chloride and methanol (90:10 by volume), and 1 liter fractions being collected. On concentrating fractions 14 to 16 to dryness, a yellow froth (15 g) is obtained, which is dissolved in hot acetonitrile (100 cc). On cooling, 2-benzhydryloxycarbonyl-7-t-butoxycarbonylamino-3-[2-(2-dimethylamino-ethylamino)-thiazol-5-yl ]-8-oxo-5-thia-1-azabicyclo[4.2.0]-oct-2-ene (3 g) is obtained in the form of white crystals (instantaneous melting point, by the Kofler method, 163° C.).

Workup

  1. washThe organic phase is washed with saturated sodium bicarbonate solution (1 liter)
  2. distillationdistilled water (1 liter) and saturated sodium chloride solution (1 liter)
  3. dry with materialis then dried over anhydrous magnesium sulphate
  4. filtrationAfter filtration, and concentration of the filtrate under reduced pressure (20 mm Hg; 2.7 kPa)
  5. customthe residue is purified by chromatography on silica gel (0.063-0.2 mm) [height of the silica layer
  6. wash38 cm, column diameter: 10 cm], elution
  7. customwith a mixture (11 liters) of methylene chloride and methanol (90:10 by volume), and 1 liter fractions being collected
  8. concentrationOn concentrating fractions 14 to 16 to dryness
  9. customa yellow froth (15 g) is obtained
  10. temperatureOn cooling

Sources & evidence

ORD record
ord-fb836ae5bef04816917341f112b64092
Source dataset
uspto-grants-1985_01
Patent number
US04496560

Reaction notes

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