Allyl bromide → HCID 67407171, compound

Temperature

-78 °C

Diisopropylamine (2.1 ml, 15 mmol) was provided in dry THF (30 ml) in argon and mixed with a solution of butyl lithium in hexane (2.5M, 6 ml, 15 mmol) at −30° C. (bath temperature). The reaction mixture was cooled to −78° C. After this temperature was reached, 4-(dimethyl-amino)-4-phenylcyclohexanone (2.17 g, 10 mmol), dissolved in dry THF (20 ml), was added in drops within 15 min. The batch was left for 30 min at −78° C. Then, allyl bromide (2.6 ml, 30 mmol), dissolved in dry THF (20 ml), was added in drops within 1 min. The reaction mixture was stirred for 10 min at −78° C., then the cooling was removed. After room temperature was reached, the batch was stirred for a further 18 h. For work up the batch was carefully mixed with water (1 ml), then saturated NH4Cl solution (40 ml) was added. The organic phase was separated and the aqueous phase was extracted with ethyl acetate (3×20 ml). The combined organic phases were washed with saturated NH4Cl solution (2×40 ml). The organic phases were then mixed with 1N HCl (30 ml) and thoroughly shaken out. The acid aqueous phase was separated and the organic phase was washed with water (2×20 ml). The combined aqueous phases were washed with ethyl acetate (1×30 ml). The aqueous solution was then placed on 2 N NaOH (70 ml). An oil separated out of the alkaline solution. The formed mixture was extracted with ethyl acetate (3×30 ml). The combined organic phases were dried over Na2SO4 and then concentrated to low volume. The more non-polar diastereoisomer of the ketone was isolated from the residue (2 g) with a yield of 540 g (22%) by means of chromatographic purification [silica gel 60 (50 g); cyclohexane/ethyl acetate 1:10 (700 ml)]. The more polar diastereoisomer was obtained with a yield of 470 mg (19%).

1. additionwas added in drops within 15 min
2. additionwas added in drops within 1 min
3. customthe cooling was removed
4. customAfter room temperature
5. stirringthe batch was stirred for a further 18 h
6. additionFor work up the batch was carefully mixed with water (1 ml)
7. additionsaturated NH4Cl solution (40 ml) was added
8. customThe organic phase was separated
9. extractionthe aqueous phase was extracted with ethyl acetate (3×20 ml)
10. washThe combined organic phases were washed with saturated NH4Cl solution (2×40 ml)
11. additionThe organic phases were then mixed with 1N HCl (30 ml)
12. stirringthoroughly shaken out
13. customThe acid aqueous phase was separated
14. washthe organic phase was washed with water (2×20 ml)
15. washThe combined aqueous phases were washed with ethyl acetate (1×30 ml)
16. customAn oil separated out of the alkaline solution
17. extractionThe formed mixture was extracted with ethyl acetate (3×30 ml)
18. dry with materialThe combined organic phases were dried over Na2SO4
19. concentrationconcentrated to low volume

ORD record

ord-cb0b41b6a1e3405bbf1210c40d8051e7

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08293758B2