Chlorotrimethylsilane → HCID 67076250, compound

To a mixture of 7.3 g (0.112 g-atom) of zinc powder (−325 mesh) and 120 mL of anhydrous tetrahydrofuran was added 10.7 mL (0.084 mole) of chlorotrimethylsilane in one portion. After stirring for 20 minutes, a solution of 10.8 mL (0.084 mole) of ethyl bromodifluoroacetate in 10 mL of tetrahydrofuran was added dropwise at a rate to keep the internal temperature below 35 degrees. The mixture was stirred for 20 minutes and then cooled to −10 to 0 degrees. A solution of 14.8 g (0.056 mole) of benzotriazol-1-ylmethyl-(trans-2-phenyl-cyclopropyl)-amine in 60 mL of tetrahydrofuran was added dropwise at a rate to keep the internal temperature at −10 to 0 degrees. After 10 minutes the reaction mixture was warmed to room temperature and stirred for 3 hours at room temperature. The solution was cooled to −10 to 0 degrees and quenched by the addition of saturated aqueous sodium bicarbonate at a rate to maintain the internal temperature −10 to 0 degrees. Ether was added, the mixture was stirred for 15 minutes at room temperature and then filtered through Celite, washing with ether. The filtrate was extracted 3 times with ether. The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. Ether and hexane were added to the residue, the solids were removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with hexane-ethyl acetate (gradient, 100:0-80:20) to give 1.7 g of 2,2-difluoro-3-(trans-2-phenyl-cyclopropylamino)-propionic acid ethyl ester as a oil.

1. customthe internal temperature below 35 degrees
2. stirringThe mixture was stirred for 20 minutes
3. temperaturecooled to −10 to 0 degrees
4. customat −10 to 0 degrees
5. stirringstirred for 3 hours at room temperature
6. temperatureThe solution was cooled to −10 to 0 degrees
7. customquenched by the addition of saturated aqueous sodium bicarbonate at a rate
8. temperatureto maintain the internal temperature −10 to 0 degrees
9. additionEther was added
10. stirringthe mixture was stirred for 15 minutes at room temperature
11. filtrationfiltered through Celite
12. washwashing with ether
13. extractionThe filtrate was extracted 3 times with ether
14. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
15. filtrationfiltered
16. concentrationconcentrated under reduced pressure
17. additionEther and hexane were added to the residue
18. customthe solids were removed by filtration
19. concentrationthe filtrate was concentrated under reduced pressure
20. customThe residue was purified by silica gel chromatography
21. washeluting with hexane-ethyl acetate (gradient, 100:0-80:20)

ORD record

ord-dce9e8833c104b0b90f7f28d1ebc9227

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08003785B2