反应详情

757 mg magnesium were stirred into 15 ml analytical grade diethyl ether under a nitrogen atmosphere and approximately one third of the solution of 4.05 g 2-fluorobenzyl chloride in 15 ml analytical grade diethyl ether was added. The remainder of the solution was rapidly added dropwise after the Grignard formation had started, and when the addition had ended the mixture was subsequently stirred for one hour, 3.60 g 4-benzyl-4-dimethylaminocyclohexanone, dissolved in 40 ml analytical grade diethyl ether, were then added dropwise and the reaction mixture was stirred overnight. For working up, 31 ml ammonium chloride solution (20 per cent by weight) were added, while cooling with ice, the phases were separated, the aqueous phase was extracted twice with 40 ml diethyl ether each time, the combined organic phases were washed with 30 ml water and extracted three times with 40 ml dilute hydrochloric acid (5 per cent by weight) each time, the combined aqueous extracts were washed with 30 ml diethyl ether, adjusted to pH 9 with ammonia solution (25 per cent by weight) and extracted three times with 40 ml methylene chloride each time, the combined methylene chloride extracts were dried over sodium sulfate, filtered and concentrated and the residue was largely freed from solvent residues in vacuo. The crude product obtained (5.02 g) was chromatographed over silica gel with diethyl ether/hexane (v/v=1:1). 2.44 g of the nonpolar diastereoisomer of 4-benzyl-4-dimethylamino-1-(2-fluorobenzyl)cyclohexanol were obtained, from which 2.53 g of the corresponding hydrochloride were prepared as described for example 4.

1. additionThe remainder of the solution was rapidly added dropwise after the Grignard formation
2. additionwhen the addition
3. additionwere then added dropwise
4. stirringthe reaction mixture was stirred overnight
5. temperaturewhile cooling with ice
6. customthe phases were separated
7. extractionthe aqueous phase was extracted twice with 40 ml diethyl ether each time
8. washthe combined organic phases were washed with 30 ml water
9. extractionextracted three times with 40 ml dilute hydrochloric acid (5 per cent by weight) each time
10. washthe combined aqueous extracts were washed with 30 ml diethyl ether
11. extractionextracted three times with 40 ml methylene chloride each time
12. dry with materialthe combined methylene chloride extracts were dried over sodium sulfate
13. filtrationfiltered
14. concentrationconcentrated
15. customThe crude product obtained (5.02 g)
16. customwas chromatographed over silica gel with diethyl ether/hexane (v/v=1:1)