Methanol → HCID 67392881, compound

HRID 456019Notes

Reaction equation

HRID 456019 reaction equation
[C:1]([O:5][C:6]([C:8]([S:11][C:12]1[S:13][CH:14]=[C:15]([C:17]([OH:19])=[O:18])[N:16]=1)([CH3:10])[CH3:9])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH2:21](N=C=NCCCN(C)C)C.CO>C(Cl)Cl.CN(C)C1C=CN=CC=1>[CH3:21][O:18][C:17]([C:15]1[N:16]=[C:12]([S:11][C:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])([CH3:10])[CH3:9])[S:13][CH:14]=1)=[O:19]

Participants

6

Reactant 3

HCID 887MethanolHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 59759410HCID 59759410, compound

Product 1

HCID 67392881HCID 67392881, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

2-(1-tert-Butoxycarbonyl-1-methyl-ethylsulfanyl)-thiazole-4-carboxylic acid was dissolved in methylene chloride (1200 mL), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (191.70 g), 4-dimethylaminopyridine (5.86 g) and methanol (19.47 mL) were added and the mixture was stirred at room temperature overnight. The mixture was washed with dilute hydrochloric acid (about 0.5 mol/L), saturated aqueous sodium hydrogen carbonate solution, and saturated aqueous sodium chloride solution (each 500 mL), and dried over anhydrous sodium sulfate. The solvent was evaporated and the residue was dissolved again in ethyl acetate (700 mL), washed successively with dilute hydrochloric acid (about 0.2 mol/L), saturated aqueous sodium hydrogen carbonate solution, and saturated aqueous sodium chloride solution (each 300 mL), and dried over anhydrous sodium sulfate. The solvent was evaporated and the obtained solid was washed with a mixed solvent (10:1, about 500 mL) of hexane and ethyl acetate, and the solid was collected by filtration. The solvent was evaporated from the filtrate and the residue was purified by silica gel column chromatography (using 500 g of Fuji Silysia BW-300, elution solvent: hexane/ethyl acetate=3/1). The obtained solid was washed with hexane and combined with the solid obtained earlier to give 2-(1-tert-butoxycarbonyl-1-methyl-ethylsulfanyl)-thiazole-4-carboxylic acid methyl ester (94.6 g).

Workup

  1. washThe mixture was washed with dilute hydrochloric acid (about 0.5 mol/L), saturated aqueous sodium hydrogen carbonate solution, and saturated aqueous sodium chloride solution (each 500 mL), and
  2. dry with materialdried over anhydrous sodium sulfate
  3. customThe solvent was evaporated
  4. dissolutionthe residue was dissolved again in ethyl acetate (700 mL)
  5. washwashed successively with dilute hydrochloric acid (about 0.2 mol/L), saturated aqueous sodium hydrogen carbonate solution, and saturated aqueous sodium chloride solution (each 300 mL), and
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent was evaporated
  8. washthe obtained solid was washed with a mixed solvent (10:1, about 500 mL) of hexane and ethyl acetate
  9. filtrationthe solid was collected by filtration
  10. customThe solvent was evaporated from the filtrate
  11. customthe residue was purified by silica gel column chromatography (using 500 g of Fuji Silysia BW-300, elution solvent: hexane/ethyl acetate=3/1)
  12. washThe obtained solid was washed with hexane
  13. customobtained earlier

Sources & evidence

ORD record
ord-5ec471b63cad45cbac89bda81a04f29f
Source dataset
uspto-grants-2013_07
Patent number
US08497382B2

Reaction notes

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