Ethyl bromoacetate → HCID 67466838, compound

Temperature

23 °C

A dried four-necked 750 ml round-bottom flask equipped with mechanical stirrer, reflux condenser, internal thermometer and septum was charged with activated zinc powder (30.6 g, 468 mmol) and copper(I) chloride (4.64 g, 47 mmol), the two solids were mixed under a slow stream of nitrogen while the flask was dried with a heat gun. After cooling to 23° C., dry THF (90 ml) was added to produce a dark slurry, heated to reflux and stirred vigorously for 30 min. The heating bath was removed and a solution of ethyl bromoacetate (12.95 ml, 117 mmol) in dry THF (50 ml) was added at such rate that reflux was reinitiated and a controllable reflux was maintained. Once addition was complete, the mixture was stirred for 30 min at 50° C. Cooled to 5° C., a solution of (R)-2-methyl-propane-2-sulfinic acid [1-(2-fluoro-5-bromo-phenyl)-(E)-ethylidene]-amide (intermediate A2B) (15.0 g, 47 mmol) in dry THF (60 ml) was added dropwise and the mixture was stirred at 0° C. for 1 h. The reaction mixture was filtered through dicalite, washed with TBME, the filtrate was washed with 5% citric acid, sat. NaHCO3-sol. and brine, dried over Na2SO4. Removal of the solvent in vacuum left the crude title compound as an orange oil (20.3 g, 106%), which was used in the next step without further purification. MS (ISP): m/z=408.0 [(M+H)+] and 410.1 [(M+2+H)+].

1. customA dried four-necked 750 ml round-bottom flask equipped with mechanical stirrer
2. temperaturereflux condenser
3. additionthe two solids were mixed under a slow stream of nitrogen while the flask
4. customwas dried with a heat gun
5. additiondry THF (90 ml) was added
6. customto produce a dark slurry
7. temperatureheated
8. temperatureto reflux
9. customThe heating bath was removed
10. temperaturethat reflux
11. temperaturea controllable reflux
12. temperaturewas maintained
13. additionOnce addition
14. stirringthe mixture was stirred for 30 min at 50° C
15. temperatureCooled to 5° C.
16. stirringthe mixture was stirred at 0° C. for 1 h
17. filtrationThe reaction mixture was filtered through dicalite
18. washwashed with TBME
19. washthe filtrate was washed with 5% citric acid, sat. NaHCO3-sol
20. dry with materialand brine, dried over Na2SO4
21. customRemoval of the solvent in vacuum
22. waitleft the crude title compound as an orange oil (20.3 g, 106%), which
23. customwas used in the next step without further purification

ORD record

ord-c1fe1ba447d8481d9b36276089dadf55

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08748418B2