Triethylamine → 3-((Tert-butoxycarbonyl)(methyl)amino)propyl methanesulfonate

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Reaction Steps

tert-Butyl (3-hydroxypropyl)methylcarbamate (551 mg, 2.92 mmol) was dissolved in dichloromethane (15 mL), triethylamine (0.811 mL, 5.83 mmol) and methanesulfonyl chloride (0.337 mL, 4.38 mmol) were added under ice cooling, and the mixture was stirred at the same temperature for 30 minutes. After the reaction was completed, a saturated aqueous sodium hydrogencarbonate solution was added, the mixture was extracted with methylene chloride, and the resulting organic layer was dried with anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, the resulting residue was purified by short-path silica gel column chromatography (elution solvents, n-hexane:ethyl acetate=1:1→0:1, v/v) to give crude 3-([tert-butoxycarbonyl)(methyl)amino]propyl methanesulfonate as a colorless oily substance. The resulting crude product was dissolved in ethanol (15 mL), N,N-diisopropylethylamine (5.07 mL, 29.2 mmol) and methoxyamine hydrochloride (2.43 g, 29.2 mmol) were added, and the mixture was stirred at 50° C. for 14 hours. After the reaction was completed, a saturated aqueous sodium hydrogencarbonate solution was added, the mixture was extracted with methylene chloride, and the resulting organic layer was dried with anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by NH silica gel column chromatography (elution solvents, n-hexane:ethyl acetate:methanol=9:1:0→0:1:0→0:9:1, v/v/v) to give the title compound (362 mg; yield, 19%).

Provenance & Evidence