Hydrogen Peroxide → HCID 86672011, compound

A solution of borane (1 M in tetrahydrofuran, 4.58 mL) was added to a solution of phenylmethyl 2-(3,4-difluorophenyl)-4-methylidenepiperidine-1-carboxylate (0.79 g, 2.3 mmol) in tetrahydrofuran (20 mL) at 0° C. The reaction mixture was slowly warmed to room temperature and stirred for 18 hours. The mixture was then cooled to 0° C., and 2M sodium hydroxide solution (2.6 mL, 5.2 mmol) then hydrogen peroxide solution (30% in water, 1.2 mL) were added sequentially. The mixture was warmed to room temperature and stirred for 1.5 hours. The reaction mixture was quenched with saturated sodium bicarbonate solution (10 mL), diluted with water (20 mL), and partitioned with ethyl acetate (20 mL). The organic portion was separated and washed twice with saturated sodium bisulfite solution (20 mL), water, then brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography (20% to 90% ethyl acetate in hexanes gradient) to give (±)-phenylmethyl (2R,4S)-2-(3,4-difluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylate (0.57 g, 69% yield), MS (EI) for C20H21F2NO3: 362 (MH+).

1. temperatureThe mixture was then cooled to 0° C.
2. temperatureThe mixture was warmed to room temperature
3. stirringstirred for 1.5 hours
4. customThe reaction mixture was quenched with saturated sodium bicarbonate solution (10 mL)
5. additiondiluted with water (20 mL)
6. custompartitioned with ethyl acetate (20 mL)
7. customThe organic portion was separated
8. washwashed twice with saturated sodium bisulfite solution (20 mL), water
9. dry with materialbrine, dried over sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated
12. customThe residue was purified by silica gel chromatography (20% to 90% ethyl acetate in hexanes gradient)

ORD record

ord-767254e69b6d4b60b0008e2a54fc429a

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08637499B2