Triethylamine → HCID 67015690, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of N-(tert-butoxycarbonyl)-D,L-alanine (1.70 g, 8.98 mmol) and triethylamine (1.25 mL, 8.98 mmol) in THF (10 mL) was added 2-methylpropyl chlorocarbonate (1.16 mL, 8.98 mmol) under ice-cooling, and the mixture was stirred for 30 min. To this solution was added a solution of methyl 4-amino-3-({3-[(2-ethylhexyl)oxy]-3-oxopropyl}sulfanyl)benzoate (3.00 g, 8.16 mmol) obtained in Reference Example 82 in THF (4 mL) under a nitrogen atmosphere, and the mixture was heated under reflux at 80° C. for 16 hr. After being allowed to cool to room temperature, the reaction mixture was diluted with ethyl acetate, and the mixture was washed with 0.5N hydrochloric acid, 10% aqueous potassium carbonate solution and saturated brine, and dried over anhydrous sodium sulfate. This solution was applied to basic silica gel column chromatography (ethyl acetate). The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=19:1 to 7:3) to give methyl 4-{[N-(tert-butoxycarbonyl)alanyl]amino}-3-({3-[(2-ethylhexyl)oxy]-3-oxopropyl}sulfanyl)benzoate (1.66 g). To the obtained oil (1.66 g, 3.08 mmol) was added trifluoroacetic acid (15 mL), and the mixture was stirred for 10 min. The reaction mixture was concentrated under reduced pressure. Ethyl acetate was added to the residue, and the mixture was washed with 10% aqueous potassium carbonate solution and saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to give methyl 4-(alanylamino)-3-({3-[(2-ethylhexyl)oxy]-3-oxopropyl}sulfanyl)benzoate (1.32 g). To a solution of this oil (1.32 g, 3.01 mmol) in ethyl acetate (15 mL) was added acetic anhydride (0.437 mL, 4.62 mmol) at room temperature and the mixture was stirred for 30 min. The solvent was evaporated under reduced pressure, and the residue was dissolved in ethyl acetate. The solution was purified by basic silica gel column chromatography (ethyl acetate) and the obtained residue was triturated with hexane to give the title compound (1.04 g, yield 70%).

Provenance & Evidence