1,2-Dibromoethane → HCID 178451182, compound

Temperature

65 °C

A 4-L flask fitted with a condenser, temperature probe and mechanical stirrer was charged with Zn metal (180.0 g, 2.76 mol, 30-100 mesh) and THF (1.25 L). While stirring 1,2-dibromoethane (4.74 mL, 0.06 mol) was added via syringe [alternatively, TMS Cl (0.1 eq.) at room temperature for one hour may be substituted]. After inert gas purge (3N2/vacuum cycles) the suspension of zinc in THF was heated to reflux (65° C.) and maintained at this temperature for 1 hour. The mixture was cooled to 50° C. before charging tert-butyl bromoacetate (488 g, 369 mL, 2.5 mol) via 50 mL syringe and syringe pump (delivery set to 4.1 mL/min) over 1.5 hours. Reaction temperature of 50°+/−50° C. was maintained throughout the addition. The reaction mixture was allowed to stir at 50° C. for one hour after the addition was complete. Subsequently, the mixture was allowed to cool to 25° C. and the precipitated product allowed to settle. The THF mother liquor is decanted into a 2-L round bottom flask using a coarse fritted filter stick and partial vacuum transfer (20 mm Hg). This removed about 65% of the THF from the mixture. 1-Methyl-2-pyrrolidinone (NMP, 800 mL) was added and agitation resumed for 5 minutes. The reaction mixture can be filtered to remove any remaining zinc. Analysis indicated a titer of desired Reformatski reagent of 1.57 M with a molar yield of 94%. Alternatively, the solid reagent can be isolated by filtration from the original reaction mixture. The cake was washed with THF until a white solid was obtained and dried under N2 to obtain the desired product as a mono THF solvate that may be stored at −20° C. (desicated) for extended periods. Typical recoveries are 85-90%.

1. customA 4-L flask fitted with a condenser
2. customAfter inert gas purge (3N2/vacuum cycles)
3. additionthe suspension of zinc in THF
4. temperaturewas heated
5. temperaturemaintained at this temperature for 1 hour
6. temperatureThe mixture was cooled to 50° C.
7. customover 1.5 hours
8. customReaction temperature of 50°+/−50° C.
9. temperaturewas maintained throughout the addition
10. additionafter the addition
11. temperatureto cool to 25° C.
12. customThe THF mother liquor is decanted into a 2-L round bottom flask
13. addition1-Methyl-2-pyrrolidinone (NMP, 800 mL) was added
14. waitagitation resumed for 5 minutes
15. filtrationThe reaction mixture can be filtered
16. customto remove any remaining zinc
17. customAlternatively, the solid reagent can be isolated by filtration from the original reaction mixture
18. washThe cake was washed with THF until a white solid
19. customwas obtained
20. customdried under N2

ORD record

ord-48fd0d28fa66489b99781d5b839c1f30

Source dataset

uspto-grants-2004_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06689754B1