ethyl N-ethoxycarbonyliminocarbamate → HCID 21058145, compound

HRID 2216432Notes

Reaction equation

HRID 2216432 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 15.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of (2S,4S)-3-acetyl-5,5-dimethyl-2-phenyl-4-thiazolidinecarboxylic acid [compound described in Reference Example 4 (b)] (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. 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, and ethyl acetate was evaporated under reduced pressure. A mixed solvent (ethanol/diisopropyl ether=200 ml/1000 ml) was added to the residue, the residue was dissolved by heating, and then the solution was allowed to stand at room temperature overnight. The precipitated crystals were filtered off and dried to give 34.7 g of the target compound. The mother liquor was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (mobile phase: hexane/ethyl acetate=1/1) to give further 43.8 g of the target compound (total 43%).

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. customwas evaporated under reduced pressure
  9. additionA mixed solvent (ethanol/diisopropyl ether=200 ml/1000 ml) was added to the residue
  10. dissolutionthe residue was dissolved
  11. temperatureby heating
  12. filtrationThe precipitated crystals were filtered off
  13. customdried

Sources & evidence

ORD record
ord-92ca0dc8c8b74dcca77af57f176eca5e
Source dataset
uspto-grants-2006_09
Patent number
US07112598B2

Reaction notes

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