O.Cl.C(OC([N:10]1[CH2:15][CH2:14][CH:13]([N:16]([CH2:21][C:22]2[S:26][C:25]([Cl:27])=[N:24][C:23]=2[Cl:28])[CH2:17][CH:18]([CH3:20])[CH3:19])[CH2:12][CH2:11]1)=O)(C)(C)C>C1COCC1>[CH3:19][CH:18]([CH3:20])[CH2:17][N:16]([CH2:21][C:22]1[S:26][C:25]([Cl:27])=[N:24][C:23]=1[Cl:28])[CH:13]1[CH2:14][CH2:15][NH:10][CH2:11][CH2:12]1To a mixture of water (850 ml) and concentrated hydrochloric acid (240 ml) is added a solution of 4-{[(2,4-dichloro-thiazol-5-yl)methyl]-isobutyl-amino}-piperidine-1-carboxylic acid t-butyl ester (304.5 g, 0.72 mol) in THF (600 ml) dropwise at 65° C. The addition and reaction are complete in 40 minutes. THF is then stripped under vacuum; residual aqueous layer is extracted with 2 L MTBE (to remove remaining (2,4-dichloro-thiazol-5-yl)-methanol). Neutralized by addition of NaOH (30%, 200 ml) and extracted twice with MTBE (1.5 L). Combined organic layers are washed with brine (3 L) then clarified (to remove insoluble). The organic layer is then concentrated under vacuum to afford 220 g of N-(2-methylpropyl)-N-[(2,4-dichloro-1,3-thiazol-5-yl)methyl]piperidin-4-amine as a pink powder. Yield 95% (HPLC=99% area). Mass spectrum (ion spray): m/z=322 (M+1); 1H NMR (400 MHz, CDCl3): δ=3.73 (2H, s), 3.17 (2H, m), 2.56 (3H, m). 2.31 (2H, d), 2.17 (1H, s, NH), 1.76 (2H, m), 1.68 (1H, m), 1.46 (2H, m), 0.92 (6H, d); 13C NMR (100 MHz, CDCl3): δ=20.6, 27.09, 28.88, 46.39, 47.20, 58.10, 58.52, 131.88, 137.30, 150.13.
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