Epibatidine (1a), a unique alkaloid isolated from the skin of the Ecuadoran poison frog Epipedobates tricolor, is a potent analgesic agent whose effects are mediated via neuronal nicotinic acetylcholine receptors (nAChRs). Previous studies on (+)- and (-)-[3H]norchloroepibatidine ([3H]NCEPB, 1c) showed higher levels of specific in vivo binding to nAChRs compared to 1a, suggesting that exo-2-(2′-fluoro-5′-pyridinyl)-7-azabicyclo[2.2.1]heptane (1b, norchlorofluoroepibatidine, NFEP) might have favorable binding properties and its 18F analog could serve as a positron emission tomography (PET) ligand for nAChR characterization. In this report, we developed an efficient synthesis of 1b (adaptable for 1a synthesis) by modifying Clayton and Regan's route, using an N-tert-butyloxycarbonyl protecting group for mild deprotection: (p-tolylsulfonyl)acetylene (5) reacted with N-(tert-butoxycarbonyl)pyrrole (6) to give diene 7, which was reduced to olefin 8; desulfonation of 8 yielded 7-(tert-butoxycarbonyl)-7-azabicyclo[2.2.1]hept-2-ene (9), which coupled with 2-amino-5-iodopyridine (4b) to form 10; diazotization of 10 in pyridine/HF afforded 1b. We also synthesized 7-(tert-butyloxycarbonyl)-2-exo-[2′-(N,N,N-trimethylammoniumyl)-5′-pyridinyl]-7-azabicyclo[2.2.1]heptane iodide (2) as a more efficient precursor for [18F]-1b (70% radiochemical yield) than previous analogs. Competition binding experiments showed 1b had a Kapp value of 0.020 nM, over 300 times more potent than nicotine (6.2 nM). [18F]-1b demonstrated high brain uptake (12-15% in baboons), high in vivo specificity for nAChRs, and a high thalamus-to-cerebellum ratio (4.0-4.5 in baboons at 2 h), providing a high signal-to-noise ratio for PET imaging. In summary, we developed efficient syntheses of 1b and 1a, and 2 is an excellent precursor for [18F]-1b, which offers a new PET tool for studying nAChRs in neurodegeneration and addiction.