(5-Ethyl-1-azabicyclo(2.2.2)octan-2-yl)(6-methoxyquinolin-4-yl)methanol → HCID 178436994, compound

Temperature

50 °C

H2O2 (30% in H2O; 0.15 mL, 1.5 mmol) was added dropwise over about 1 min to a stirred solution of hydroquinine (163 mg, 0.5 mmol), 3-iodooxetane (184 mg, 1.0 mmol), concentrated H2SO4 (54 μL, 1.0 mmol) and iron(II) sulfate heptahydrate (40 mg, 0.15 mmol) in DMSO (5 mL) at room temperature. After addition of the H2O2 the mixture was placed in an oil bath at 50 °C. After 2 min a further portion of iron(II) sulfate heptahydrate (40 mg, 0.15 mmol) was added and the mixture was stirred at 50 °C for 35 min. Further iron(II) sulfate heptahydrate (40 mg, 0.15 mmol) and H2O2 (30% in H2O; 0.15 mL, 1.5 mmol) was added and the mixture was stirred at 50 °C for a further 15 min then allowed to cool. The mixture was poured into a 0.2 M solution of NaOH (15 mL) and Et2O (30 mL). Saturated NaHCO3 was added to bring the pH to 10. The aqueous and organic layers were partitioned and the aqueous layer was extracted with Et2O (2 x 15 mL). The combined organic extracts were washed with brine (2 x 15 mL). The combined aqueous phases were extracted with additional Et2O (15 mL) [NB this was undertaken as some product was noted to still be in all the aqueous phase]. The combined organic extracts were dried (MgSO4), filtered and the solvent removed under vacuum to leave a crude oil (186 mg). The oil was purified by preparative high-performance liquid chromatography (column: Gemini C18 10 μM; size: 150 x 21.2 mm; eluent: 20-75% MeCN in 10 mM aqueous Et2NH or 35-98% MeCN in 10 mM aqueous Et2NH; run time: 17 min; flow rate: 20 mL/min; detection: UV at 254 nM) to give the desired product - 17 -5b collected as four aliquots (1st aliquot 12 mg, ca. 90% purity, 6% yield; 2nd aliquot 19 mg, ca. 80% purity, 8% yield; 3rd aliquot 17 mg, ca. 80% purity, 7% yield; 4th aliquot 12 mg, ca. 90% purity, 6% yield. All yields have been adjusted for purities). Total yield = 27% (yield adjusted for purity). The 1stand 4th aliquots were purified further by preparative high-performance liquid chromatography (column: Gemini C18 10 μM; size: 150 x 21.2 mm; eluent: 55-95% MeOH in 10 mM aqueous Et2NH; run time: 20 min; flow rate: 20 mL/min; detection: UV at 254 nM) to give material for data purposes

ORD record

ord-079d5ee961d349b3860c3cad94f9eab1

Source dataset

Minisci dataset from Roche

DOI

10.1021/jo9010624