Methyl dithiocarbamate → HCID 20430429, compound

HRID 2413419Notes

Reaction equation

HRID 2413419 reaction equation
[C:1](=[S:5])([S:3][CH3:4])[NH2:2].[CH:6]([O:19][C:20]([C:22]1[N:23]2[CH:26]([S:27][CH2:28][C:29]=1[CH:30](Br)[CH:31]=O)[CH:25]([NH:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[C:24]2=[O:42])=[O:21])([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1>O1CCCC1.C(O)C.O.C(OCC)(=O)C>[CH:6]([O:19][C:20]([C:22]1[N:23]2[CH:26]([S:27][CH2:28][C:29]=1[C:30]1[S:5][C:1]([S:3][CH3:4])=[N:2][CH:31]=1)[CH:25]([NH:34][C:35]([O:37][C:38]([CH3:39])([CH3:40])[CH3:41])=[O:36])[C:24]2=[O:42])=[O:21])([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

7

Reactant 2

HCID 4995032Methyl dithiocarbamateHCID 13175928HCID 13175928, compound

Product 1

HCID 20430429HCID 20430429, compoundYield 16.4%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
66 °C

Procedure

A solution of methyl dithiocarbamate (9 g) in tetrahydrofuran (250 cc) is heated to the reflux temperature, and 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 (44 g) in ethanol (100 cc) is then added. The reaction mixture is heated at 66° C. for 65 minutes and is then diluted with water (2 liters) and ethyl acetate (1 liter). The aqueous phase is decanted and washed with ethyl acetate (250 cc). The combined organic phases are washed with a half-saturated sodium chloride solution (1 liter), then dried over sodium sulphate, and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C. The residue is chromatographed on a column (diameter: 8 cm) of silica gel (0.2-0.06 mm) (1 liter), 500 cc fractions being collected. Elution is carried out successively with methylene chloride (3.5 liters) and with a 90:10 (by volume) mixture of methylene chloride and ethyl acetate (8 liters). Fractions 14 to 16, containing the pure product, are combined and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C. The residue is triturated with isopropyl ether and is then filtered off and dried; 2-benzhydryloxycarbonyl-7-t-butoxycarbonylamino-3-(2-methylthio-thiazol-5-yl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (7.3 g) is obtained in the form of a cream-coloured solid.

Workup

  1. customThe aqueous phase is decanted
  2. washwashed with ethyl acetate (250 cc)
  3. washThe combined organic phases are washed with a half-saturated sodium chloride solution (1 liter)
  4. dry with materialdried over sodium sulphate
  5. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C
  6. customThe residue is chromatographed on a column (diameter: 8 cm) of silica gel (0.2-0.06 mm) (1 liter), 500 cc fractions
  7. custombeing collected
  8. washElution
  9. additionis carried out successively with methylene chloride (3.5 liters) and with a 90:10 (by volume) mixture of methylene chloride and ethyl acetate (8 liters)
  10. additionFractions 14 to 16, containing the pure product
  11. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C
  12. customThe residue is triturated with isopropyl ether
  13. filtrationis then filtered off
  14. customdried

Sources & evidence

ORD record
ord-50e3d646c5b6481f8da4ad9d3b3ae6ae
Source dataset
uspto-grants-1985_01
Patent number
US04496560

Reaction notes

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