Ammonium Chloride → HCID 66661054, compound

CuBr (24.54 g, 168 mmol, 1.2 eq.) and LiBr (29.18 g, 336 mmol, 2.4 eq.) were initially charged in a baked-out flask under argon, then dissolved in 600 ml of absolute THF and stirred at RT for 20 min. This gave a clear yellow-orange solution. The mixture was then cooled to −78° C., and MeMgCl solution (55.46 ml, 168 mmol, 1.2 eq.) was added dropwise thereto. This led to a yellow suspension which was difficult to stir, so that a further 75 ml of THF were added dropwise; the mixture was subsequently stirred at −60° C. for 15 min. The carbonyl chloride from example 12 dissolved in about 150 ml of THF (41.67 g, 140 mmol) was initially stirred at −60° C. and then slowly added dropwise. The reaction mixture thus formed was stirred at this temperature for 1 h. The workup was effected by adding about 100 ml of saturated NH4Cl solution; the mixture was stirred vigorously at −60° C. for 10 min, then 200 ml of heptane and 60 ml of water were added and the mixture was stirred at RT for a further 15 min. The phases were separated, and the aqueous phase was admixed with 50 ml of 1 M HCl (green solution) and extracted twice with about 100 ml of ethyl acetate. The combined organic phases were washed with 2 M HCl solution, saturated NaHCO3 and saturated NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. Subsequently, purification was effected by means of silica gel flash chromatography (5:1-2:1 heptane/ethyl acetate); production fractions were combined and freed of solvent residues under reduced pressure. Yield: 21.6 g, 56% of theory

1. customThis gave a clear yellow-orange solution
2. temperatureThe mixture was then cooled to −78° C.
3. additionwere added dropwise
4. stirringthe mixture was subsequently stirred at −60° C. for 15 min
5. stirringwas initially stirred at −60° C.
6. additionslowly added dropwise
7. customThe reaction mixture thus formed
8. stirringwas stirred at this temperature for 1 h
9. stirringthe mixture was stirred vigorously at −60° C. for 10 min
10. stirringthe mixture was stirred at RT for a further 15 min
11. customThe phases were separated
12. extractionextracted twice with about 100 ml of ethyl acetate
13. washThe combined organic phases were washed with 2 M HCl solution, saturated NaHCO3 and saturated NaCl solution
14. dry with materialdried over sodium sulfate
15. concentrationconcentrated under reduced pressure
16. customSubsequently, purification

ORD record

ord-44daf8b3a0f2447c94ee593ddb0bcb30

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08609681B2