Methanol → Methyl 3-fluoromethyl-5-hydroxymethylbenzoate

Dimethyl 5-fluoromethylisophthalate (33) (3.16 g, 14.0 mmol) was dissolved in THF (10.5 mL). The air was evacuated from the reaction system, and then Ar was charged therein. To the solution were added NaBH4 (638 mg, 16.9 mmol), and then a mixted solution of THF:MeOH (8.8 mL:2.6 mL) slowly dropwise. The reaction mixture was refluxed for 1 hour. TLC was used to confirm the progress of the reaction. Then, the reaction was quenched with HCl (1 N, 14 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. The residue was purified by neutral silica gel column chromatography (hexane:EtOAc=5:1 to 2:1) to isolate methyl 3-fluoromethyl-5-hydroxymethylbenzoate (34) (2.21 g, 80%) as white crystals.

1. customThe air was evacuated from the reaction system
2. additionAr was charged
3. temperatureThe reaction mixture was refluxed for 1 hour
4. customthe progress of the reaction
5. customThen, the reaction was quenched with HCl (1 N, 14 mL)
6. extractionThe mixture was extracted with EtOAc
7. washThe organic layer was washed with a saturated sodium chloride aqueous solution
8. dry with materialdried over anhydrous sodium sulfate
9. customevaporated under reduced pressure
10. customThe residue was purified by neutral silica gel column chromatography (hexane:EtOAc=5:1 to 2:1)

ORD record

ord-18cebb2628424d1c93711dd52da84bce

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08633304B2