Water → Tert-butyl 5-(methoxymethylthio)-2-methylpentan-2-ylcarbamate

Participants

Reaction Steps

The tert-butyl 5-hydroxy-2-methylpentan-2-ylcarbamate (743 mg) obtained in Reference Example 239 was dissolved in pyridine (10 mL). To the solution, methanesulfonyl chloride (320 μL) was added, and the mixture was stirred at room temperature for 1 hour. To the reaction mixture, water (20 mL) was added, and the resultant mixture was then extracted with ethyl acetate (20 mL×4). The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was co-evaporated with toluene (10 mL×3), and the residue was then dissolved in DMF (13 mL). To the mixture, potassium carbonate (1.42 g) and thioacetic acid (490 μL) were added, and the mixture was stirred at room temperature for 2.5 hours. To the reaction mixture, water (25 mL) was added, and the resultant mixture was then extracted with ethyl acetate (25 mL). The organic layer was washed with water (20 mL) and brine (20 mL), dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue was dissolved in methanol (10 mL). To the mixture, sodium methoxide (369 mg) was added, and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure, an aqueous saturated ammonium chloride solution (15 mL) was then added thereto, and the resultant mixture was then extracted with ethyl acetate (20 mL×2). The organic layer was washed with brine (10 mL), dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue was dissolved in dichloromethane (5.0 mL). To the mixture, N,N-diisopropylethylamine (2.08 mL) and chloromethyl methyl ether (650 μL) were added, and the mixture was stirred at room temperature for 4 hours. To the reaction mixture, an aqueous saturated ammonium chloride solution (10 mL) was added, and the resultant mixture was then extracted with ethyl acetate (10 mL). The organic layer was washed with an aqueous saturated ammonium chloride solution (10 mL) and brine (10 mL), dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (15% ethyl acetate/hexane) to obtain the title compound (788 mg) as a colorless oil.

Provenance & Evidence