Tetrahydrofuran → HCID 10108892, compound

Participants

Reaction Steps

757 mg magnesium were stirred into 15 ml analytical grade tetrahydrofuran under a nitrogen atmosphere and approximately one third of the solution of 5.69 g 1-(2-bromoethyl)-3-fluorobenzene in 16 ml analytical grade tetrahydrofuran 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 16 ml analytical grade tetrahydrofuran, 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 (3.96 g) was chromatographed over silica gel with diethyl ether/hexane (v/v=1:1). 301 mg of the nonpolar diastereoisomer of 4-benzyl-4-dimethylamino-1[2-(4-fluorophenyl)ethyl]cyclohexanol were obtained, from which 254 mg of the corresponding hydrochloride were prepared as described for example 4.

Provenance & Evidence