Hydrochloric Acid → methyl (1S,2S)-2-((benzyloxy)methyl)cyclopropanecarboxylate

Sodium hydride (60%, oil, 0.907 g, 22.68 mmol) was added to a solution of methyl (1S,2S)-2-(hydroxymethyl)cyclopropanecarboxylate (2.27 g, 17.44 mmol) in THF (110 mL) at 0° C. under argon atmosphere. The reaction mixture was stirred at room temperature for 1 hr, and cooled to 0° C. To the reaction mixture were added benzyl bromide (2.70 mL, 22.68 mmol) and tetra-n-butylammonium iodide (0.644 g, 1.74 mmol), and the mixture was stirred at room temperature for 15 hr. The reaction mixture was poured into cooled 0.5N hydrochloric acid (350 mL), and the mixture was extracted with ethyl acetate (×3). The organic layer was washed with water and brine, and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent gradient; 2→25% ethyl acetate/hexane) to give methyl (1S,2S)-2-((benzyloxy)methyl)cyclopropanecarboxylate (1.38 g, 6.27 mmol, 36%) as a colorless oil.

1. temperaturecooled to 0° C
2. stirringthe mixture was stirred at room temperature for 15 hr
3. additionThe reaction mixture was poured
4. extractionthe mixture was extracted with ethyl acetate (×3)
5. washThe organic layer was washed with water and brine
6. dry with materialdried over magnesium sulfate
7. customthe solvent was evaporated under reduced pressure
8. customThe obtained residue was purified by silica gel column chromatography (solvent gradient; 2→25% ethyl acetate/hexane)

ORD record

ord-c822c80337ea4e50b4d6028d9182fc96

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09365520B2