N,N-Diethylethanamine trihydrofluoride → Benzyl 4-(difluoromethyl)piperidine-1-carboxylate

To a cooled (0° C.) solution of XtalFluor-E (4.50 g, 19.65 mmol) in dichloromethane (50 mL) was added a solution of 4-formyl-N-CBZ-piperidine (2.30 g, 9.30 mmol, Oakwood) in dichloromethane (7 mL) followed by triethylamine trihydrofluoride (3.00 mL, 18.40 mmol). The reaction was allowed to warm to room temperature overnight. Then the reaction mixture was cooled to 0° C. and quenched slowly with saturated NaHCO3 solution. The layers were separated and the aqueous layer was extracted with dichloromethane (3×). The combined organic layers were evaporated onto silica gel and purified by flash chromatography (Isco 40 g) eluting with (EtOAc):hexanes (0:1→1:1) to give benzyl 4-(difluoromethyl)piperidine-1-carboxylate as a light-yellow oil (1.16 g, 46% yield).

1. temperatureThen the reaction mixture was cooled to 0° C.
2. customquenched slowly with saturated NaHCO3 solution
3. customThe layers were separated
4. extractionthe aqueous layer was extracted with dichloromethane (3×)
5. customThe combined organic layers were evaporated onto silica gel
6. custompurified by flash chromatography (Isco 40 g)
7. washeluting with (EtOAc)

ORDレコード

ord-4ef457703be64b36afaa5837f5e69feb

出典データセット

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09296734B2