Toluene → HCID 11543494, compound

Participants

Reaction Steps

Powdered sodium hydroxide (3.36 g, 84 mmol) was dissolved in water (5.6 mL) and cooled to room temperature. Intermediate (d) (R)-1-chloro-3-(4-fluoro-3-trifluoromethylphenyl)-2-propanol (assumed 13 mmol) was added as a solution in methanol (13.3 mL in total) and the mixture stirred for 5 minutes at room temperature. 2-aminoethane hydrogen sulfate (7.90 g, 56 mmol) was added in one portion and the resultant mixture warmed to 40° C. (bath temperature) for 2 hrs. Toluene (35 mL) and sodium hydroxide (powdered 3.36 g, 84 mmol) were added and the reaction heated at 65° C. (bath temperature) for 18 hrs, with vigorous stirring. The reaction was allowed to cool to room temperature and poured into water (80 mL), layers separated and the aqueous layer extracted with ethyl acetate (40 mL×2). Combined organic layers were washed with brine (30 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (silica; triethylamine/ethanol ethanol/ethyl acetate, 1/20/79 ratio) yielded the desired intermediate (c), (R)-2-(4-fluoro-3-trifluoromethylbenzyl)morpholine, as yellow oil (2.34 g).

Provenance & Evidence