alpha-Bromo-o-fluorotoluene → 1-tert-Butyl 3-methyl 3-(2-fluorobenzyl)piperidine-1,3-dicarboxylate

Temperature

-78 °C

In a flask, lithium bis(trimethylsilyl)amide (LHMDS) (9.24 mL of 1.0 M solution in THF, 9.24 mmol) was added to tetrahydrofuran (20 mL). The reaction mixture was cooled to −78° C., and then a solution of 1-tert-butyl 3-methyl piperidine-1,3-dicarboxylate (1.5 g, 6.17 mmol) in tetrahydrofuran (5 mL) was added drop-wise to the reaction mixture at −78° C. The reaction was stirred at −78° C. for 30 minutes. Afterwards, 2-fluorobenzylbromide (1.12 mL, 9.24 mmol) was added, and the reaction was stirred for an additional 3 hours at 0° C. Upon reaction completion, the reaction was quenched with saturated ammonium chloride solution (50 mL) and extracted three times with ethyl acetate (50 mL). The organic layers were combined, dried with sodium sulfate, and concentrated to yield crude product. The crude product was purified using flash chromatography (0-60% ethyl acetate in hexane) to give the titled compound (1.41 g).

1. stirringthe reaction was stirred for an additional 3 hours at 0° C
2. customUpon reaction completion
3. customthe reaction was quenched with saturated ammonium chloride solution (50 mL)
4. extractionextracted three times with ethyl acetate (50 mL)
5. dry with materialdried with sodium sulfate
6. concentrationconcentrated
7. customto yield crude product
8. customThe crude product was purified

ORD record

ord-4dffbf0f3588488cb1c3c14d2321b420

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09351965B2