ethyl N-ethoxycarbonyliminocarbamate → HCID 21058145, compound

HRID 2216431Notes

Reaction equation

HRID 2216431 reaction equation
[C:1]([N:4]1[C@@H:8]([C:9]([OH:11])=[O:10])[C:7]([CH3:13])([CH3:12])[S:6][C@H:5]1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)(=[O:3])[CH3:2].[C:20]([N:23]1[C:27]2[CH:28]=[CH:29][C:30]([Cl:32])=[CH:31][C:26]=2[S:25][CH:24]1[C:33]1[CH:38]=[C:37]([O:39][CH3:40])[CH:36]=[CH:35][C:34]=1O)(=[O:22])[CH3:21].N(C(OCC)=O)=NC(OCC)=O>CN(C=O)C>[C:20]([N:23]1[C:27]2[CH:28]=[CH:29][C:30]([Cl:32])=[CH:31][C:26]=2[S:25][CH:24]1[C:33]1[CH:38]=[C:37]([O:39][CH3:40])[CH:36]=[CH:35][C:34]=1[O:10][C:9]([C@H:8]1[C:7]([CH3:13])([CH3:12])[S:6][C@@H:5]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[N:4]1[C:1](=[O:3])[CH3:2])=[O:11])(=[O:22])[CH3:21]

Participants

5

Reactant 3

HCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 2825757HCID 2825757, compoundHCID 14053536HCID 14053536, compound

Product 1

HCID 21058145HCID 21058145, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of (2S,4S)-3-acetyl-5,5-dimethyl-2-phenyl-4-thiazolidinecarboxylic acid (102 g, 0.38 mol) in anhydrous DMF (500 ml) was added to a solution of 3-acetyl-6-chloro-2-(2-hydroxy-5-methoxyphenyl)benzothiazoline (127 g, 0.38 mol) in anhydrous DMF (500 ml) at room temperature. N,N-Dimethylaminopyridine (5.58 g, 45.7 mmol) was added thereto under a nitrogen atmosphere at room temperature with stirring. After ice-cooling, diethyl azodicarboxylate (87 g, 0.50 mol) was added thereto, and then the mixture was stirred under ice-cooling for 15 minutes, at room temperature for one hour and further at an internal temperature of about 40° C. for three days. The reaction mixture was concentrated under reduced pressure, a 10% aqueous citric acid solution (1,000 ml) was added to the residue, and the whole was extracted with ethyl acetate (1,000 ml). The organic layer was washed with water (1,000 ml) and saturated brine (1,000 ml) successively and dehydrated with magnesium sulfate. Ethyl acetate was evaporated under reduced pressure, a mixed solvent (ethanol/diisopropyl ether=200 ml/1,000 ml) was added to the residue, the residue was dissolved by heating, and then the solution was allowed to stand at room temperature overnight. One precipitated diastereomer was filtered out, and the mother liquor was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (mobile phase: hexane/ethyl acetate=1/1) to give 78.0 g (43%) of the target compound.

Workup

  1. temperatureAfter ice-cooling
  2. stirringthe mixture was stirred under ice-
  3. temperaturecooling for 15 minutes, at room temperature for one hour and further at an internal temperature of about 40° C. for three days
  4. concentrationThe reaction mixture was concentrated under reduced pressure
  5. additiona 10% aqueous citric acid solution (1,000 ml) was added to the residue
  6. extractionthe whole was extracted with ethyl acetate (1,000 ml)
  7. washThe organic layer was washed with water (1,000 ml) and saturated brine (1,000 ml) successively
  8. customEthyl acetate was evaporated under reduced pressure
  9. additiona mixed solvent (ethanol/diisopropyl ether=200 ml/1,000 ml) was added to the residue
  10. dissolutionthe residue was dissolved
  11. temperatureby heating
  12. filtrationOne precipitated diastereomer was filtered out
  13. concentrationthe mother liquor was concentrated under reduced pressure
  14. customThe residue was purified by silica gel column chromatography (mobile phase: hexane/ethyl acetate=1/1)

Sources & evidence

ORD record
ord-fe47cb7b26ca47109b4c6aa4bd8e19b0
Source dataset
uspto-grants-2006_09
Patent number
US07112598B2

Reaction notes

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