Acetyl chloride → HCID 66790341、化合物

To 450 mL of methanol at 0° C. was carefully added 30 mL of acetyl chloride and the resulting solution was allowed to stir at ambient temperature for 30 min. The resulting solution was added to 27 g (86 mmol) of dimethyl 2-cyano-3-(2,4,5-trifluorophenyl)pentanedioate from Step B and the reaction mixture was then shaken with 5.0 g of platinum (IV) oxide under 50 psi of hydrogen for 20 h. The mixture was filtered through a pad of Celite and the filter cake washed with methanol and dichloromethane. The combined filtrate and washings were concentrated and then taken up in 400 mL of 1:1 methanol/toluene with potassium carbonate (28 g, 200 mmol). The resulting mixture was heated to reflux for 4 h, then cooled to 0° C. and carefully quenched with 1N hydrochloric acid until the solution was acidic by pH paper. The resulting mixture was then extracted with six 300-mL portions of 3:1 chloroform/isopropyl alcohol and the organic phases combined and washed with saturated aqueous brine (300 mL). The organic phase was then dried over magnesium sulfate, filtered, and evaporated in vacuo to yield a colorless solid. This crude material was dissolved in 500 mL of 1:1 diethyl ether/methanol and cooled to 0° C. To this solution was added 75 mL (150 mmol) of trimethylsilyldiazomethane solution (2M in hexanes) in portions until a yellow color persisted. After warming to ambient temperature, the solution was stirred an additional 2 h, then concentrated in vacuo. The title compound was collected as a colorless crystalline solid which was used without further purification. LC/MS 288.3 (M+1).

1. customat 0° C.
2. filtrationThe mixture was filtered through a pad of Celite
3. washthe filter cake washed with methanol and dichloromethane
4. concentrationThe combined filtrate and washings were concentrated
5. temperatureThe resulting mixture was heated
6. temperatureto reflux for 4 h
7. temperaturecooled to 0° C.
8. customcarefully quenched with 1N hydrochloric acid until the solution
9. extractionThe resulting mixture was then extracted with six 300-mL portions of 3:1 chloroform/isopropyl alcohol
10. washwashed with saturated aqueous brine (300 mL)
11. dry with materialThe organic phase was then dried over magnesium sulfate
12. filtrationfiltered
13. customevaporated in vacuo
14. customto yield a colorless solid
15. temperaturecooled to 0° C
16. temperatureAfter warming to ambient temperature
17. stirringthe solution was stirred an additional 2 h
18. concentrationconcentrated in vacuo
19. customThe title compound was collected as a colorless crystalline solid which
20. customwas used without further purification

ORDレコード

ord-fd96d7a6cce8461b8f5ac54011f6e2d4

出典データセット

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07884104B2