Nitrogen → HCID 23433578, compound

Temperature

140 °C

To a flame dried 250 mL 3-necked rb flask equivuipped with a magnetic stir bar was added Ce(III) Cl.7 H2O (2.74 g, 7.35 mmol, 2 equiv). The flask was heated in a 140° C. oil bath under reduced pressure (~1 torr) for 2.5 h. The flask was cooled to rt and slowly filled with N2 g. The white powder was suspended in dry THF (30 mL), stirred at rt for 1 h and then cooled to -78° C. To the white suspension was added a 1.4M solution of methyl lithium (MeLi) in Et2O (5.25 mL, 7.35 mmol, 2 equiv) by syringe. The dark yellow/brown solution stirred at -78° C. for 1 h and then 1-t-butoxycarbonyl-1,2,3,4-tetrahydro-7-methoxy-4-quinolone dissolved in 3 mL THF was added. The solution stirred at -78° C. for 3 h and was warmed to 0° C. for 2 h. The reaction did not go to completion and starting material was observed by TLC (silica gel, hexane/EtOAc, 3:1). The reaction was quenched with H2O (1 mL) and allowed to warm to rt. The solution was neutralized with sat NH4Cl solution (5 mL), extracted with EtOAc (3×100 mL), washed with brine (1×100 mL), dried over Na2SO4 and concentrated in vacuo to give a mix of the desired alcohol and starting material. The mixture was taken up in EtOAc and concentrated on CeliteTM to give a free flowing powder which was purified via flash column chromatography (silica gel, hexanes/EtOAc, 3:1) to give 796 mg (74%) of the desired product as a vicious clear colorless oil. Data for 1-t-butoxycarbonyl-1,2,3,4-tetrahydro-4-hydroxy-4-methyl-7-methoxy-quinoline: Rf =0.20 (hexanes/EtOAc, 3:1); 1H NMR (400 MHz, CDCl3) 7.42 (d, J=8.7, 1 H), 7.33 (d, J=2.5, 1 H), 6.66 (dd, J=2.5, 8.6, 1 H), 3.98 (m, 1 H), 3.79 (s, 3 H, OCH3), 3.61 (m, 1 H), 1.98 (m, 2 H), 1.58 (s, 3 H), 1.53 (s, 9 H).

1. customTo a flame dried 250 mL 3-necked rb flask
2. customequivuipped with a magnetic stir bar
3. additionwas added Ce(III) Cl
4. temperatureThe flask was cooled to rt
5. temperaturecooled to -78° C
6. stirringThe dark yellow/brown solution stirred at -78° C. for 1 h
7. additionwas added
8. stirringThe solution stirred at -78° C. for 3 h
9. temperaturewas warmed to 0° C. for 2 h
10. customThe reaction was quenched with H2O (1 mL)
11. temperatureto warm to rt
12. extractionextracted with EtOAc (3×100 mL)
13. washwashed with brine (1×100 mL)
14. dry with materialdried over Na2SO4
15. concentrationconcentrated in vacuo
16. customto give
17. concentrationconcentrated on CeliteTM
18. customto give
19. customwas purified via flash column chromatography (silica gel, hexanes/EtOAc, 3:1)

ORD record

ord-00677ae889c548bc97747801d00db4ef

Source dataset

uspto-grants-1997_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05693646