3-Fluoroadamantane-1-carboxylic acid → 3,5-Difluoroadamantane-1-carboxylic acid

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Reaction Steps

The procedure of Example 2 for the conversion of 3-fluoroadamantane-1-carboxylic acid to 3-fluoroadamantan-1ylamine was utilized. 4.32 g (20 mmol) of 3,5-difluoroadamantane-1-carboxylic acid provided after 96 hours crude product which was chromatographed on silica gel using 4:1 hexane:EtOAc to afford 4.7 g (73%) of benzyl carbamate: mp 71.9-72.9° C.; 1H NMR (CDCl3) 1.80-1.90 (7H, m), 2.02-2.25 (6H, m) 2.40-2.50 (1H, m), 4.84 (1H, bs),5.04 (2H, bs), 7.30-7.40 (5H, m); 13C NMR (CDCl3) 29.07, 38.98, 40.15, 45.54, 47.16, 54.25, 66.37, 92.24 (188.67), 128.09, 128.17, 128.52, 128.56, 136.26, 154.18. Anal. Calc'd for C18H2NO2F2 : C, 67.27; H, 6.59; N, 4.36; F, 11.82; Found: C, 66.96; H, 6.54; N, 4.33; F, 11.71. Hydrogenation (HOAc/Pd/C/50 PSI) of 7.84 g (24.4 mmol) of this intermediate for a period of 5 hours provided 7.8 g (>100%) of 3, 5-difluoro-adamantan-1ylamine as its acetate salt.

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