Water → HCID 53446371, compound

Temperature

-78 °C

Lithium hexamethyldisilazide (1M in tetrahydrofuran, 15.7 mL, 15.7 mmol) was added dropwise to a stirred, cooled (−78° C.) solution of 1-(1,1-dimethylethyl) 4-phenylmethyl 1,4-piperidinedicarboxylate (2.50 g, 7.83 mmol) in tetrahydrofuran (50 mL) and the mixture was stirred at −78° C. for 2 hours. 4-Bromo-1-butene (1.99 mL, 19.6 mmol) was added dropwise and the mixture was stirred at −78° C. for 1 hour, then at room temperature for 2 hours. Water (100 mL) was added and the mixture was extracted with ethyl acetate (2×100 mL). The combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with isohexane/EtOAc (90:10) to give the title compound (1.07 g, 37%). 1H NMR (400 MHz CDCl3) δ 7.4–7.3 (5H, m), 5.75–5.6 (1H, m), 5.15 (2H, s), 4.93 (1H, br d, J 7 Hz), 4.90 (1H, br s), 3.95–3.75 (2H, m), 2.93–2.78 (2H, m), 2.13 (2H, br d, J 10 Hz), 1.95–1.85 (2H, m), 1.65–1.55 (2H, m), 1.44 (9H, s), and 1.43–1.30 (2H, m).

1. stirringthe mixture was stirred at −78° C. for 1 hour
2. waitat room temperature for 2 hours
3. extractionthe mixture was extracted with ethyl acetate (2×100 mL)
4. dry with materialThe combined organic fractions were dried (MgSO4)
5. customthe solvent was evaporated under reduced pressure
6. customThe residue was purified by flash column chromatography on silica gel
7. washeluting with isohexane/EtOAc (90:10)

ORD record

ord-8cf16cbefa77473bae626586e5ed824c

Source dataset

uspto-grants-2006_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07105507B2