Diisopropylamine → HCID 23557501, compound

Temperature

0 °C

A solution of 0.32 mL (2.2 mmol) of diisopropylamine in 10 mL of THF at 0° C. was treated with 0.92 mL (2.3 mmol) of 2.5 M n-butyllithium in sol'n in hexanes. The resulting solution was stirred at 0° C. for 10 min, then cooled to −78° C. A solution of 0.51 g (1.8 mmol) of (1-tert-butoxycarbonylpiperidin-4-yl)acetic acid, ethyl ester (from Piperidine 35, Step A) in 2 mL of THF was added. After stirring for 30 minutes, a solution of 0.26 g (2.1 mmol) 5-chloropentanal in 2 mL of THF was added (J. Org. Chem. 1981, 46, 2007). The reaction was stirred for 1.75 hours at −78° C. and 3.5 hours at 0° C. After quenching the reaction with saturated NH4Cl, volatiles were removed under reduced pressure. The residue was partitioned between 100 mL of Et2O and 100 mL of H2O. After separating phases, the organic layer was washed with 100 mL of 0.5 N HCl and 100 mL of 1 N NaHCO3, dried over MgSO4 and concentrated. The residue was purified with a 40M Biotage column using 3:1 v/v of hexanes/EtOAc as the eluant to afford impure title compound: RF: 0.27 (7:3 v/v hexanes/EtOAc); 1H-NMR (500 MHz) δ 1.24–2.08 (m, 23H), 2.38 (t, J=6.2, 1H), 2.63–2.71 (m, 2H), 3.53–3.56 (m, 2H), 3.92 (m, 1H), 4.09–4.19 (m, 4H).

1. temperaturecooled to −78° C
2. stirringAfter stirring for 30 minutes
3. stirringThe reaction was stirred for 1.75 hours at −78° C. and 3.5 hours at 0° C
4. customAfter quenching
5. customthe reaction with saturated NH4Cl, volatiles
6. customwere removed under reduced pressure
7. customThe residue was partitioned between 100 mL of Et2O and 100 mL of H2O
8. customAfter separating phases
9. washthe organic layer was washed with 100 mL of 0.5 N HCl and 100 mL of 1 N NaHCO3
10. dry with materialdried over MgSO4
11. concentrationconcentrated
12. customThe residue was purified with a 40M Biotage column

ORD record

ord-d303685f2cb944afb45e8d3181ca39cb

Source dataset

uspto-grants-2006_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07125887B2