Sodium bis(trimethylsilyl)amide → (R)-tert-butyl 2-vinylpiperidine-1-carboxylate

Temperature

0 °C

NaHMDS (1.0 M in THF, 18.6 mL, 18.6 mmol) was slowly added over 15 min to a 0° C. solution of methyltriphenylphosphonium bromide (7.19 gm, 20.1 mmol) in THF (65 mL). The yellow mixture was stirred at 0° C. for 45 min and then cooled to −78° C. A solution of (R)-tert-butyl 2-formylpiperidine-1-carboxylate (3.30 gm, 15.5 mmol) in THF (10 mL) was added dropwise. The reaction mixture was then stirred at 0° C. for 1 hr. The reaction was quenched by the addition of saturated aqueous NH4Cl. The solution was partitioned between EtOAc and water. The aqueous phase was isolated and extracted with EtOAc. All organic phases were combined, dried over MgSO4, filtered and concentrated. The crude product was purified using silica gel chromatography (ISCO system) eluting with a gradient of 0-100% EtOAc/Hex to give (R)-tert-butyl 2-vinylpiperidine-1-carboxylate (2.53 gm, 12.0 mmol, 77% yield) as an orange oil. Anal. Calcd. for C12H21N0 m/z 211.3. found: 212.0 (M+H)+.

1. temperaturecooled to −78° C
2. stirringThe reaction mixture was then stirred at 0° C. for 1 hr
3. customThe reaction was quenched by the addition of saturated aqueous NH4Cl
4. customThe solution was partitioned between EtOAc and water
5. customThe aqueous phase was isolated
6. extractionextracted with EtOAc
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated
10. customThe crude product was purified
11. washeluting with a gradient of 0-100% EtOAc/Hex

ORD record

ord-854fa071a0ff4c908d67eba87d336ffc

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09346852B2