Triethylsilane → HCID 10452233, compound

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Reaction Steps

Under argon, 4-fluorobenzaldehyde (149 mg, 1.2 mmol) and dimethyl(1-phenyl-4-trimethylsilanyloxymethylcyclohexyl)amine (306 mg, 1 mmol) were dissolved in abs. DCM (20 ml) and cooled to 0° C. Trimethylsilyl triflate (387 μl, 2 mmol) was added dropwise at 0° C. and the mixture was stirred for 60 min at this temperature, after which triethylsilane (319 μl, 2 mmol) was added dropwise at 0° C. With slow heating to RT, the mixture was stirred overnight. For the work-up, DCM (10 ml) and 1 M NaOH (5 ml) were added and the mixture was stirred vigorously for 15 min. The organic phase was separated off, washed with 1 M NaOH (2×2 ml) and with water (1×2 ml), dried, filtered and concentrated. The residue was purified by chromatography on silica gel [40 g of silica gel 60; eluent: 600 ml of EE/MeOH (1:1) and 600 ml of MeOH/conc. NH3 (400:1)]. The two diastereoisomers of [4-(4-fluorobenzyloxymethyl)-1-phenylcyclohexyl]dimethylamine were isolated (17 mg of less polar diastereoisomer (yellow oil) and 106 mg of more polar diastereoisomer (yellow oil)). 75 mg of the more polar diastereoisomer were dissolved in 2-butanone (2 ml), with heating, chlorotrimethylsilane (83.4 μl) was added dropwise at RT and the mixture was stirred for 2 h. The solvent was completely distilled off and the residue was covered with a layer of dry ether and mechanically detached from the wall of the flask. The resulting solid was filtered off with suction, washed with ether (4×2 ml) and dried to give 79 mg of the hydrochloride of the more polar diastereoisomer of [4-(4-fluorobenzyloxymethyl)-1-phenylcyclohexyl]-dimethylamine (greyish-white solid, m.p. 176-181° C.).

Provenance & Evidence