Methanol → 3-Azidomethyl-5-fluoromethylbenzylalcohol

Participants

Reaction Steps

Methyl 3-azidomethyl-5-fluoromethylbenzoate (35) (468 mg, 2.10 mmol) was dissolved in THF (1.5 mL). The air was evacuated from the reaction system, and then Ar was charged therein. To the solution were added NaBH4 (97.5 mg, 2.58 mmol), and then a mixed solution of THF:MeOH (1.3 mL:0.4 mL) slowly dropwise. The reaction mixture was refluxed for 20 hour. TLC was used to confirm the progress of the reaction. Then, the reaction was quenched with 1N hydrochloric acid (2.5 mL). The mixture was extracted with EtOAc. The organic layer was washed with a saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to remove the solvent. The residue was purified by neutral silica gel column chromatography (hexane:EtOAc=5:1, then EtOAc) to isolate 3-azidomethyl-5-fluoromethylbenzylalcohol (36) (149 mg, 36%) as a colorless oil. In addition, the aqueous layer of the extraction was basified with a saturated sodium hydrogen carbonate aqueous solution and extracted with EtOAc. The organic layer was washed with a saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to give methyl 3-aminomethyl-5-fluoromethylbenzoate (37) (33.1 mg, 8%) as a yellow clear oil.

Provenance & Evidence