Pyridine → 6,9,9-Trimethoxy-2-methyl-5-(3-methylbut-2-en-1-yl)-2-(4-methylpent-3-en-1-yl)tricyclo[3.3.1.01,3]non-6-en-8-one

Temperature

0 °C

A DCM (2.3 mL) solution of 25 (47.7 mg, 0.12 mmol, 1 equiv.) and pyridine (57 μL, 0.70 mmol, 6 equiv.) was cooled to −40° C. in a 10-mL recovery flask, and trifluoromethanesulfonic anhydride (99 μL, 0.59 mmol, 5 equiv.) was added dropwise. The yellow slurry was allowed to slowly warm to 0° C. over 45 min, whereupon it was quenched at 0° C. with saturated aqueous NaHCO3. The mixture was extracted thrice with EtOAc. The combined organic extracts were washed with H2O and brine, dried over Na2SO4, filtered, and concentrated in vacuo to a brown oil, which was used without further purification due to its propensity to decompose upon standing. A THF (1 mL) solution of this brown oil was cooled to −78° C. in a 10-mL test tube, and a freshly prepared THF solution of lithium diethylamide (0.50 M, 1.2 mL, 0.59 mmol, 5 equiv.) was added. The resulting brown-orange solution was allowed to slowly warm to 0° C. over 40 min and stirred at 0° C. for 10 min. At this time, chlorotrimethylsilane (150 μL, 1.2 mmol, 10 equiv.) was added. The red solution subsequently turned bright orange and was stirred at 0° C. for 15 min. The solution was then quenched at 0° C. with saturated aqueous NaHCO3 and extracted thrice with EtOAc. The organic extracts were combined, washed with H2O and brine, dried over Na2SO4, filtered, and concentrated in vacuo to a brown oil. Flash column chromatography (30 mL SiO2, 9:1 to 8:2 hexane:EtOAc) afforded 16.5 mg (42 μmol, 35% yield over 2 steps) of 26 as a yellow oil. TLC Rf 0.39 (8:2 hexane:EtOAc). TLC Rf 0.39 (8:2 hexane:EtOAc). 1H NMR (500 MHz; C6D6): δ 5.58 (t, J=6.9 Hz, 1H), 5.50 (t, J=7.2 Hz, 1H), 5.45 (s, 1H), 3.05 (s, 3H), 3.02 (s, 3H), 3.01 (s, 3H), 2.87-2.79 (m, 2H), 2.37 (m, 2H), 1.99 (dd, J=13.4, 6.6 Hz, 1H), 1.87 (td, J=12.3, 5.2 Hz, 1H), 1.79 (s, 3H), 1.77-1.73 (m, 2H), 1.70 (s, 6H), 1.60 (s, 3H), 1.56 (s, 3H), 0.89 (t, J=7.0 Hz, 1H).

1. customwas quenched at 0° C. with saturated aqueous NaHCO3
2. extractionThe mixture was extracted thrice with EtOAc
3. washThe combined organic extracts were washed with H2O and brine
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo to a brown oil, which
7. customwas used without further purification due to its propensity
8. temperatureA THF (1 mL) solution of this brown oil was cooled to −78° C. in a 10-mL test tube
9. temperatureto slowly warm to 0° C. over 40 min
10. stirringThe red solution subsequently turned bright orange and was stirred at 0° C. for 15 min
11. customThe solution was then quenched at 0° C. with saturated aqueous NaHCO3
12. extractionextracted thrice with EtOAc
13. washwashed with H2O and brine
14. dry with materialdried over Na2SO4
15. filtrationfiltered
16. concentrationconcentrated in vacuo to a brown oil

ORD record

ord-fc4ea814748a463983c8954211bf0a26

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09321713B2