tert-Butyl 4-oxopiperidine-1-carboxylate → Tert-butyl 4-(3-((tert-butyldimethylsilyl)oxy)prop-1-yn-1-yl)-4-hydroxypiperidine-1-carboxylate

Temperature

-78 °C

To a solution of tert-butyldimethyl(prop-2-yn-1-yloxy)silane (0.5 mL, 2.46 mmol) in 30 mL of anhydrous THF was added dropwise n-BuLi (1.2 mL, 2.95 mmol) at −78° C. under N2. After stirring for 1 h at −78° C., tert-butyl 4-oxopiperidine-1-carboxylate (588.4 mg, 2.95 mmol) in THF (2 mL) was added dropwise to the above solution at −78° C. under N2. The resulting mixture was stirred at −78° C. under N2 for 2 h, then allowed to warm to r.t. and stirred for another 1.5 h. The reaction mixture was cooled to −78° C. and quenched by sat. NH4Cl aq., and the resulting mixture was extracted with EtOAc (50 mL, 30 mL). The combined organic phase was washed with brine, dried over anhy. Na2SO4 and concentrated in vacuo to afford 1.10 g of title compound. LC-MS: m/z 370.7 (M+H)+. 1H NMR (CHLOROFORM-d) δ: 4.37 (s, 2H), 3.74 (d, J=6.2 Hz, 2H), 3.35-3.24 (m, 2H), 2.46 (t, J=6.2 Hz, 1H), 1.92-1.84 (m, 2H), 1.71 (ddd, J=12.9, 9.1, 3.8 Hz, 2H), 1.47 (s, 9H), 0.92 (s, 9H), 0.13 (s, 6H).

1. stirringThe resulting mixture was stirred at −78° C. under N2 for 2 h
2. temperatureto warm to r.t.
3. stirringstirred for another 1.5 h
4. temperatureThe reaction mixture was cooled to −78° C.
5. customquenched by sat. NH4Cl aq.
6. extractionthe resulting mixture was extracted with EtOAc (50 mL, 30 mL)
7. washThe combined organic phase was washed with brine
8. customdried over anhy
9. concentrationNa2SO4 and concentrated in vacuo

ORD record

ord-7e1c637882434e0cb74e90e009a945a7

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09365545B2