Acetylthiourea → HCID 13175939, compound

HRID 2413402Notes

Reaction equation

HRID 2413402 reaction equation
[C:1]([NH:4][C:5]([NH2:7])=[S:6])(=[O:3])[CH3:2].[CH:8]([O:21][C:22]([C:24]1[N:25]2[CH:28]([S:29][CH2:30][C:31]=1[CH:32](Br)[CH:33]=O)[CH:27]([NH:36][C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[C:26]2=[O:44])=[O:23])([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>O1CCCC1.C(OCC)(=O)C.C(=O)(O)[O-].[Na+]>[C:1]([NH:4][C:5]1[S:6][C:32]([C:31]2[CH2:30][S:29][CH:28]3[N:25]([C:26](=[O:44])[CH:27]3[NH:36][C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[C:24]=2[C:22]([O:21][CH:8]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)=[O:23])=[CH:33][N:7]=1)(=[O:3])[CH3:2]

Participants

6

Reactant 2

HCID 2723593AcetylthioureaHCID 13175928HCID 13175928, compound

Product 1

HCID 13175939HCID 13175939, compoundYield 8.9%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
25 °C

Procedure

A solution of acetylthiourea (1.8 g) in dry tetrahydrofuran (20 cc) is added, in 5 minutes, to a solution, cooled to 3° C., of the mixture of the epimers of 2-benzhydryloxycarbonyl-7-t-butoxycarbonylamino-3-(1-bromo-2-oxoethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (5.87 g) in dry tetrahydrofuran (58.7 cc). The reaction mixture is then stirred for 4 hours 30 minutes at 25° C. after which it is diluted with ethyl acetate (150 cc) and saturated sodium bicarbonate solution (150 cc). The organic layer is washed with distilled water (2×100 cc) and then with saturated sodium chloride solution (100 cc) and dried. After evaporation of the solvent under reduced pressure (30 mm Hg; 4 kPa) at 30° C., the residue is chromatographed on a column (height: 30 cm; diameter: 6 cm) of silica (0.04-0.06 mm), elution being carried out under a pressure of 0.4 bar (40 kPa) with a 70:30 (by volume) mixture (1600 cc) of cyclohexane and ethyl acetate and then with a 30:70 (by volume) mixture (2000 cc) of cyclohexane and ethyl acetate, 100 cc fractions being collected. Fractions 27 to 33, containing the pure product, are combined and evaporated to dryness. 3-(2-Acetylamino-thiazol-5-yl)-2-benzhydryloxycarbonyl-7-t-butoxycarbonylamino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (0.54 g) is obtained in the form of a yellow froth.

Workup

  1. washThe organic layer is washed with distilled water (2×100 cc)
  2. dry with materialwith saturated sodium chloride solution (100 cc) and dried
  3. customAfter evaporation of the solvent under reduced pressure (30 mm Hg; 4 kPa) at 30° C.
  4. customthe residue is chromatographed on a column (height: 30 cm; diameter: 6 cm) of silica (0.04-0.06 mm), elution
  5. customwith a 30:70 (by volume) mixture (2000 cc) of cyclohexane and ethyl acetate, 100 cc fractions being collected
  6. additionFractions 27 to 33, containing the pure product
  7. customevaporated to dryness

Sources & evidence

ORD record
ord-8ef5d619989a4afd988aee6d907366c9
Source dataset
uspto-grants-1985_01
Patent number
US04496560

Reaction notes

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