Ammonia → HCID 131723337, compound

Participants

Reaction Steps

The base was freed from 3.2 g (11.2 mmole) of the hydrochloride of 2-[dimethylamino-(4-fluorophenyl)methyl]cyclohexanone obtained according to stage 1 with 30 ml of water and 10 ml of ammonia solution (25 vol. %), extracted three times with 30 ml of ether each time, and the combined organic extracts were dried over sodium sulfate, filtered, and concentrated by evaporation on a rotary evaporator without heating (500 to 10 mbar). 2.69 g (10.8 mmole) of this base were dissolved in 10 ml of tetrahydrofuran, added dropwise while cooling in an ice bath to 6.5 ml (12.9 mmole) of benzylmagnesium chloride (2 M solution in tetrahydrofuran), and the whole was stirred for 15 hours at RT. The reaction mixture was worked up by adding 15 ml of saturated ammonium chloride solution while cooling in an ice bath and was extracted three times at RT, with 15 ml of ether each time. The combined organic extracts were dried over sodium sulfate, filtered, and concentrated by evaporation on a rotary evaporator (500 to 10 mbar). 3.42 g of crude base (84.1% of theory) were obtained, from which a hydrochloride was precipitated according to Example 1 (3rd stage) with chlorotrimethylsilane/water in 2-butanone. The base was freed from the hydrochloride with 30 ml of water and 5 ml of ammonia solution (25 vol. %), extracted three times with 15 ml of ether each time, and the combined organic extracts were dried over sodium sulfate, filtered, and concentrated by evaporation on a rotary evaporator (500 to 10 mbar). 2.89 g of crude base (78.6% of theory) were obtained, from which 2.58 g of 1-benzyl-2-[dimethylamino-(4-fluoro-phenyl)methyl]cyclohexanol, hydrochloride (63.3% of theory) having a melting point of 178° C. were obtained according to the procedure described in Example 1 (3rd stage) with chlorotrimethylsilane/water in 2-butanone.

Provenance & Evidence