1,2-Dibromoethane → Magnesium Bromide

A solution of MgBr2 is prepared from 1,2-dibromo-ethane (6.76 g, 36 mmol, 4 eq) and magnesium (0.88 g, 36 mmol, 4 eq) in ether (80 ml) under a nitrogen atmosphere. A 2-lithio-furan solution is prepared under nitrogen atmosphere by adding a 1.6M solution of n-butyl-lithium in hexane (28 ml, 45 mmol, 5 eq) dropwise to a mixture of furan (3.1 g, 45 mmol, 5 eq) and TMEDA (5.2 g, 45 mmol, 5 eq) in anhydrous ether (100 ml) at −20° C. The mixture is then taken to reflux for 2 hours, cooled down to ambient temperature and MgBr2 in ether is added dropwise to the solution. A 1-piperidin-1-yl-cyclohexanecarbonitrile (1.7 g, 9 mmol, 1 eq) solution in ether is added dropwise at ambient temperature. The mixture is taken to reflux for 16 hours, cooled down to ambient temperature, then treated in the following manner: the mixture is poured gently into an ice-cooled saturated solution of NH4Cl, agitated for 30 minutes, extracted with ether; the ethereal phases are combined, then extracted three times with 10% HCl, and 20% NH4OH is added to the aqueous phase until neutrality. The aqueous phase is extracted with ether, the organic phase is washed with water, dried over Na2SO4, filtered and concentrated under vacuum. The crude product is purified by chromatography on alumina with CH2Cl2 as eluent in order to produce an oil (1.7 g, 76%).

1. temperatureto reflux for 2 hours
2. temperatureto reflux for 16 hours
3. temperaturecooled down to ambient temperature
4. additiontreated in the following manner
5. extractionextracted with ether
6. extractionextracted three times with 10% HCl, and 20% NH4OH
7. additionis added to the aqueous phase until neutrality
8. extractionThe aqueous phase is extracted with ether
9. washthe organic phase is washed with water
10. dry with materialdried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated under vacuum
13. customThe crude product is purified by chromatography on alumina with CH2Cl2 as eluent in order

ORD record

ord-c3e238acc68d44b4923c678d58532a7f

Source dataset

uspto-grants-2002_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06342511B1