Hydrochloric Acid → (2-{5-[2-(5-Fluoro-2-methoxy-phenyl)-ethyl]-tetrahydro-furan-2-yl}-ethyl)-methyl-amine

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Reaction Steps

Into a flame dried round bottom flask, purged with Ar(g), was placed 23 (112 mg, 0.33 mmol, 1.0 eq) and anhydrous THF (1.6 mL). The flask was cooled with an ice bath and stirred for 15 min. LAH (1.0 M, 1.32 mL, 1.32 mmol, 4.0 eq) was then slowly added via syringe over a period of 5 min. The reaction was allowed to warm to rt and stirred an additional 4 hrs. The reaction was then stopped with ice cold MeOH and then stirred for an additional 15 min at rt. The resulting solution was acidified with 1N HCl(aq) and then transferred to a beaker and then made basic with 10 M NaOH(aq). The basic solution was then extracted with diethyl ether (3×20 mL) and then the organic layer was washed with brine. The diethyl ether extract was dried over Mg2SO4 for 15 min and then filtered and concentrated to oil under reduced pressure to afford the crude product. The oil was purified with preparative TLC (developed with MeOH/CH2Cl2, 5:95, v:v, Rf 0.05); 1H NMR (CDCl3, 500 MHz) 6.87-6.82 (m, 2 H), 6.74-6.71 (m, 1 H), 4.05-3.77 (m, 2 H), 3.78 (s, 3 H), 2.71-2.56 (m, 5 H), 2.08-1.51 (m, 10 H); HRMS (ESI) [M+H]+ calcd for C16H25FNO2 282.3784, found 282.3762; HPLC>97% pure (tR=30.23 min, 100(A):0.5(D); tR=26.05 min, 90(A):10(C):0.5(D)).

Provenance & Evidence