Di-tert-butyl dicarbonate → HCID 57546011, compound
Reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([C@H:11]([O:13][CH2:14][C:15]2([C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=3)[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]2)[CH3:12])[C:8]2[C:4](=[CH:5][N:6](COCC[Si](C)(C)C)[N:7]=2)[CH:3]=1.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O>FC(F)(F)C(O)=O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C@H:11]([O:13][CH2:14][C:15]3([C:28]4[CH:29]=[CH:30][C:31]([F:34])=[CH:32][CH:33]=4)[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:26])([CH3:27])[CH3:25])=[O:22])[CH2:17][CH2:16]3)[CH3:12])[CH:10]=1)[NH:7][N:6]=[CH:5]2Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
(R)-tert-Butyl 4-((1-(5-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (850 mg, 1.375 mmol) was dissolved in trifluoroacetic acid (50% in dichloromethane, 30 mL) and stirred at room temperature for 4 h. The reaction was concentrated, loaded onto a strong cation exchange cartridge (4×2 g cartridges) in methanol, and flushed with several volumes of methanol which were discarded. The product was eluted with 2M ammonia in methanol and concentrated. The crude piperidine was dissolved in dichloromethane (10 mL), and treated with di-tert-butyl dicarbonate(0.48 mL, 2.062 mmol). The reaction was quenched by addition of ethylene diamine (200 mg) in dichloromethane (2 mL). The reaction was concentrated and purified by column chromatography (25%→37% ethyl acetate/n-hexane) to give 650 mg (97%) as a white foam solid. 1H-NMR (CDCl3, 500 MHz) δ 9.66 (bs, 1H), 7.90 (s, 1H), 7.57 (d, J=1.8 Hz, 1H), 7.26 (dd, J=8.9, 5.5 Hz, 2H), 7.07 (dd, J=8.9, 8.6 Hz, 2H), 6.98 (d, J=1.5 Hz, 1H), 4.49 (q, J=6.4 Hz, 1H), 3.74 (m, 2H), 3.38 (d, J=9.2 Hz, 1H), 3.25 (d, J=9.2 Hz, 1H), 3.22 (bs, 2H), 3.05 (m, 1H), 2.97 (m, 1H), 2.26 (m, 1H), 2.06 (m, 1H), 1.84 (m, 1H), 1.73 (m, 1H), 1.43 (m. 12H); 13C NMR (75 MHz, CDCl3) δ ppm 171.0, 161.5 (d, J=247 Hz), 154.8, 137.9, 137.8, 135.4, 133.7, 128.5 (d, J=7.5 Hz), 127.3, 125.9, 124.6, 124.0, 118.9, 115.5 (d, J=21 Hz), 79.4, 78.5, 78.1, 60.3, 41.0, 39.8 (br), 32.3, 32.0, 28.3, 22.0, 20.9, 14.1. Mass spec.: 488.17 (MH)+.