Trifluoromethanesulfonic anhydride → HCID 10904469, compound

Temperature

-78 °C

A mixture of 4-(tert-butyldimethylsilyloxymethyl)-1-(triphenylmethyl)imidazole, as described above in Step D, (485 mg, 1.07 mmol), 1-(4-cyano-3-fluorophenyl)ethanol, as described above in Step C, (160 mg, 0.969 mmol), and N,N-diisopropylethylamine (0.219 mL, 1.26 mmol) in CH2Cl2 (12 mL) was cooled to −78° C., under argon. Trifluoromethanesulfonic anhydride (0.196 mL, 1.17 mmol) was added dropwise, and the mixture was stirred for 18 hours while it slowly warmed to ambient temperature. Methanol (15 mL) was added and the CH2Cl2 was distilled off in vacuo. The resulting methanolic solution was heated to reflux for 3 hours, then concentrated in vacuo to give a residue which was partitioned between saturated aqueous Na2CO3 (10 mL) and CH2Cl2 (20 mL). The aqueous layer was extracted further with CH2Cl2 (20 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography, eluting with a gradient of CH2Cl2—0% to 5% MeOH, to yield the titled product as a pale foam.

1. temperatureslowly warmed to ambient temperature
2. distillationthe CH2Cl2 was distilled off in vacuo
3. temperatureThe resulting methanolic solution was heated
4. temperatureto reflux for 3 hours
5. concentrationconcentrated in vacuo
6. customto give a residue which
7. customwas partitioned between saturated aqueous Na2CO3 (10 mL) and CH2Cl2 (20 mL)
8. extractionThe aqueous layer was extracted further with CH2Cl2 (20 mL)
9. dry with materialThe combined organic extracts were dried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customThe residue was purified by silica gel chromatography
13. washeluting with a gradient of CH2Cl2—0% to 5% MeOH

ORD record

ord-32d20c8a81fd4ca9aa2376f52694b513

Source dataset

uspto-grants-2002_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06441017B1