4-Fluorobenzaldehyde → methyl (1S,2R,3S,4R)-3-[(4-fluorobenzyl)amino]bicyclo[2.2.1]heptane-2-carboxylate

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Reaction Conditions

Reaction Steps

Methyl (1S,2R,3S,4R)-3-[(4-Fluorobenzyl)amino]bicyclo[2.2.1]heptane-2-carboxylate Methyl (1S,2R,3S,4R)-3-aminobicyclo[2.2.1]heptane-2-carboxylate hydrochloride (0.5 g, 2.43 mmol) was dissolved in methanol (12 mL). Sodium acetate (0.4 g, 4.86 mmol) was added followed by 4 Å powdered molecular sieves (0.5 g) and 4-fluoro-benzaldehyde (0.302 g, 2.43 mmol). Sodium cyanoborohydride (0.305 g, 4.86 mmol) was added and the mixture was stirred at 25° C. for 16 h. The mixture was poured into a mixture of aqueous saturated sodium bicarbonate solution (200 mL) and ethyl acetate (300 mL). After shaking, both layers were passed through a plug of Celite. The organic phase was further washed with aqueous saturated sodium bicarbonate solution (100 mL), aqueous saturated brine solution (100 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo to afford the crude product, methyl (1S,2R,3S,4R)-3-[(4-fluorobenzyl)amino]bicyclo[2.2.1]heptane-2-carboxylate (0.663 g, 2.39 mmol, 98% yield) as a clear oil. LC-MS (ESI) calcd for C16H20FNO2 277.15. found 278.2 [M+H+] (100%).

Provenance & Evidence