(1S,3S,4R)-2-[(2-methylpropan-2-yl)oxycarbonyl]-2-azabicyclo[2.2.1]heptane-3-carboxylic acid

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 6-bromonaphthalene-1,2-diamine (1.08 g, 4.56 mmol), and (1S,3S,4R)-2-(tert-butoxycarbonyl)-2-azabicyclo[2.2.1]heptane-3-carboxylic acid (1.10 g, 4.56 mmol) and HATU (2.08 g, 5.47 mmol) in methylene chloride (45 mL) was added DIPEA (3.98 mL, 22.79 mmol). The mixture was stirred at room temperature for two hours. Upon completion, the reaction was concentrated in vacuo, diluted with ethyl acetate and washed with water. The aqueous layer was back extracted with ethyl acetate twice. The combined organic layers were washed with brine, concentrated, and purified by normal phase chromatography (30-80% ethyl acetate (5% MeOH) in hexanes) to give (1S,3S,4R)-tert-butyl 3-(1-amino-6-bromonaphthalen-2-ylcarbamoyl)-2-azabicyclo[2.2.1]heptane-2-carboxylate (2.01 g, 95%). LCMS-ESI+: calc'd for C22H26BrN3O3: 459.12 (M+); Found: 460.9 (M+H+). Upon completion, the reaction was concentrated in vacuo diluted with ethyl acetate washed with water The aqueous layer was back extracted with ethyl acetate twice The combined organic layers were washed with brine concentrated purified by normal phase chromatography (30-80% ethyl acetate (5% MeOH) in hexanes)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (1S,3S,4R)-2-tert-butyl 3-methyl 2-azabicyclo[2.2.1]heptane-2,3-dicarboxylate (1.67 g, 6.54 mmol) in THF:MeOH (41 mL:13 mL) was added aqueous Lithium hydroxide (1M, 8.2 mL, 8.2 mmol) and the reaction was allowed to stir at room temperature overnight. Upon completion, the reaction was concentrated in vacuo, diluted with ethyl acetate and washed with 1N HCl. The aqueous layer was back extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated to give (1S,3S,4R)-2-(tert-butoxycarbonyl)-2-azabicyclo[2.2.1]heptane-3-carboxylic acid (1.36 g, 86%). 1H NMR (400 MHz, Methanol-d4) δ 6.43 (s, 1H), 5.84 (s, 1H), 5.74 (d, 1H), 4.34 (s, 1H), 3.36-3.18 (m, 3H), 3.17-3.06 (m, 3H), 3.02 (s, 3H), 2.97 (s, 6H). Upon completion, the reaction was concentrated in vacuo diluted with ethyl acetate washed with 1N HCl The aqueous layer was back extracted with ethyl acetate The combined organic layers were dried over sodium sulfate filtered concentrated