Acetic Acid → HCID 67000256, compound

Temperature

0 °C

To a solution of hexamethyldisilazane (167 mL, 800 mmol) in THF (200 mL) at 0° C. was cannulated n-BuLi (500 mL, 800 mmol) and the mixture was stirred at 0° C. for 30 min, then cannulated into a solution of freshly distilled 2,2,6-trimethyl-1,3-dioxin-4-one (56.9 g, 400 mmol) in THF (400 mL) at −78° C., keeping the internal temperature below −60° C. Stirring was continued at −78° C. for 1 h, then a solution of ethyl 2,2,2-trifluoroacetate (52.5 mL, 440 mmol) in THF (100 mL) was added quickly (<1 min; internal temperature remained below −70° C.). The cooling bath was removed and stirring was continued at −78 to 0° C. for 2 h. Cooled to −45° C., then HOAc (57.3 mL, 1000 mmol) was added and the mixture was warmed to −10° C. Poured into ice cold 0.5 M HCl (pH 1), extracted with TBME, washed with sat. NaHCO3-sol., ice cold 0.5 M HCl and brine, dried over Na2SO4. Removal of the solvent in vacuum (bath temperature below 40° C.) left a yellow oil, added THF (ca. 200 mL), toluene (ca. 50 mL) and H2O (ca. 20 mL) and evaporated to dryness to give the title compound as a light yellow solid (89.27 g, 87%). MS (ISN) 237.0 [(M−H)−].

1. customat 0° C.
2. customthe internal temperature below −60° C
3. stirringStirring
4. waitwas continued at −78° C. for 1 h
5. customThe cooling bath was removed
6. stirringstirring
7. waitwas continued at −78 to 0° C. for 2 h
8. temperatureCooled to −45° C.
9. temperaturethe mixture was warmed to −10° C
10. extractionextracted with TBME
11. washwashed with sat. NaHCO3-sol
12. dry with material, ice cold 0.5 M HCl and brine, dried over Na2SO4
13. customRemoval of the solvent in vacuum (bath temperature below 40° C.)
14. waitleft a yellow oil
15. additionadded THF (ca. 200 mL), toluene (ca. 50 mL) and H2O (ca. 20 mL)
16. customevaporated to dryness

ORD record

ord-b0d857a436f94800bb2c337766119e56

Source dataset

uspto-grants-2010_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07718661B2