Triethylamine → HCID 21636547, compound

Temperature

0 °C

Add trimethylsilyl trifluoromethanesulfonate (18.5 mL, 102 mmol, 1.3 equiv.) over 5 minutes to a cold (0° C.) stirred solution of solution 6,7-dihydro-1-benothiophen-4(5H)-one (12.04 g, 79.1 mmol, 1 equiv.) and triethylamine (33 mL, 237 mmol, 3 equiv.) in dry dichloromethane (200 mL). Stir the reaction mixture at 0° C. for 5 minutes and then warm to room temperature for 1 h10 min before adding water. Separate the layers, extract the aqueous layer twice with dichloromethane, dry the combined organic extracts over anhydrous magnesium sulfate, filter, and concentrate under reduced pressure. Dissolve the resulting crude silylenol ether in anhydrous dimethylformamide (200 mL), place the reaction mixture in a room temperature water bath, and add 1-(chloromethyl)-4fluoro-1,4-diazoniabicyclo[2.2.2]octanebis(tetrafluoroborate) (Selectfluor™) (31.06 g, 87.7 mmol, 1.1 equiv.) in one portion. Stir the reaction mixture at room temperature for 15 minutes then add tetrabutylammonium fluoride (1M in THF, 87 mL, 87 mmol, 1.1 equiv.) and stir at room temperature for 1 hr before adding water and ethyl acetate. Separate the layers, extract the aqueous layer three times with ethyl acetate, wash the combined organic extracts successively with water (2 times) then 0.1N HCl (2 times), dry the combined organic extracts over anhydrous magnesium sulfate, filter, and concentrate under reduced pressure. Purify the resultant crude material by medium pressure liquid chromatography eluting with 0 to 20% ethyl acetate in hexanes to afford the title compound as an orange solid (9.725 g, 72%). δH (400 MHz, CDCl3) 2.41-2.54 (m, 1H), 2.56-2.67 (m, 1H), 3.10-3.20 (m, 1H), 3.23-3.33 (m, 1H), 5.12 (ddd, 1H, J=47, 11, 4 Hz), 7.15 (d, 1H, J=6 Hz), 7.41 (d, 1H, J=6 Hz).

1. temperaturewarm to room temperature for 1 h10 min
2. customSeparate the layers
3. extractionextract the aqueous layer twice with dichloromethane
4. dry with materialdry the combined organic extracts over anhydrous magnesium sulfate
5. filtrationfilter
6. concentrationconcentrate under reduced pressure
7. dissolutionDissolve the resulting crude silylenol ether in anhydrous dimethylformamide (200 mL)
8. customin a room temperature
9. stirringStir the reaction mixture at room temperature for 15 minutes
10. customSeparate the layers
11. extractionextract the aqueous layer three times with ethyl acetate
12. washwash the combined organic extracts successively with water (2 times)
13. dry with material0.1N HCl (2 times), dry the combined organic extracts over anhydrous magnesium sulfate
14. filtrationfilter
15. concentrationconcentrate under reduced pressure
16. customPurify the resultant crude material by medium pressure liquid chromatography
17. washeluting with 0 to 20% ethyl acetate in hexanes

ORD record

ord-140ea65e4faa44ddac1d64ee4ff27c7b

Source dataset

uspto-grants-2008_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07417064B2