[H-].[Na+].Cl[C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]([N+:14]([O-:16])=[O:15])=[CH:6][N:5]=1.[C:17]([O:21][C:22]([N:24]1[CH2:29][CH2:28][CH:27]([OH:30])[CH2:26][CH2:25]1)=[O:23])([CH3:20])([CH3:19])[CH3:18].Cl>C1COCC1.O>[C:17]([O:21][C:22]([N:24]1[CH2:29][CH2:28][CH:27]([O:30][C:4]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7]([N+:14]([O-:16])=[O:15])=[CH:6][N:5]=2)[CH2:26][CH2:25]1)=[O:23])([CH3:20])([CH3:18])[CH3:19]Add NaH (60% in mineral oil, unwashed; 6.23 g, 156 mmol) in portions to a solution of 1-chloro-4-nitroisoquinoline (26.0 g, 125 mmol) and 1-tert-butoxycarbonyl-4-hydroxypiperidine (27.6 g, 137 mmol) in THF (350 mL) stirred at room temperature under nitrogen flow. Stir the dark reddish mixture at 40° C. for 1.5 hours then 55° C. for 1.5 hours. Add additional NaH (1.3 g), and stir the resulting mixture at 55° C. for 2 hours then cool to room temperature overnight. Add hexanes (75 mL), then add water (600 mL) slowly. Adjust the reaction mixture to pH 7 with aqueous HCl (1 N), then separate layers. Discard the aqueous layer and add hexanes (200 mL) to the organic layer. Partially concentrate the mixture under reduced pressure to a volume of 50-100 mL. Add diethyl ether (150 mL) and hexanes (250 mL), then filter the resultant slurry. Wash the cake with diethyl ether/hexanes (1:1) and air-dry to provide 4-(4-nitro-isoquinolin-1-yloxy)-piperidine-1-carboxylic acid tert-butyl ester (33.84 g, 73% yield) as a tan solid. (ES+): m/z 374 (M++H).
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