Ethyl Acetate → HCID 89874622, compound

A mixture of ethyl 5-(2,2-difluoroethoxy)-4-methylpicolinate (2.0 g, 8.2 mmol, Step-2) and calcium chloride (3.62 g, 32.6 mmol) in THF-EtOH (1:1, 60 mL) is stirred at rt for 30 minutes. Then, the mixture is cooled to 0° C., and sodium borohydride (771 mg, 20.4 mmol) is added portionwise. After stirring 1 day, the reaction is quenched with saturated aqueous ammonium chloride solution (200 mL), and the aqueous layer is extracted with DCM (200 mL×2). The combined organic layer is dried over sodium sulfate, and after filtration, the filtrate is concentrated in vacuo. The residue is purified by column chromatography on silica gel eluting with n-hexane/EtOAc (10:1 then EtOAc only) to give 1.61 g (97% yield) of the title compound as white solid.

1. temperatureThen, the mixture is cooled to 0° C.
2. stirringAfter stirring 1 day
3. customthe reaction is quenched with saturated aqueous ammonium chloride solution (200 mL)
4. extractionthe aqueous layer is extracted with DCM (200 mL×2)
5. dry with materialThe combined organic layer is dried over sodium sulfate
6. filtrationafter filtration
7. concentrationthe filtrate is concentrated in vacuo
8. customThe residue is purified by column chromatography on silica gel eluting with n-hexane/EtOAc (10:1

ORD record

ord-05235bcc67de4a149c4d63d596187a87

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09187475B2