C(OC(=O)N)(C)(C)C.B(O)O.[C:12]([O:16][C:17](=[O:27])[NH:18][CH2:19][C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=1)([CH3:15])([CH3:14])[CH3:13].C(OC([NH:35][CH2:36][C:37]1[CH:38]=[CH:39][C:40](F)=C(B(O)O)C=1)=O)(C)(C)C.ClC1C=CN=CC=1.BrC1C=CN=CC=1>>[C:12]([O:16][C:17](=[O:27])[NH:18][CH2:19][C:20]1[CH:21]=[CH:22][C:23]([F:26])=[C:24]([C:38]2[CH:37]=[CH:36][N:35]=[CH:40][CH:39]=2)[CH:25]=1)([CH3:15])([CH3:13])[CH3:14]The present invention is directed to an improved method for preparing 4-fluoro-3-piperidin-4-yl-benzyl)-carbamic acid tert-butyl ester (I); more particularly, to its synthesis in three steps. The first step comprises a boronic acid formation by treatment of (4-fluoro-benzyl)-carbamic acid tert-butyl ester under boronation conditions. The second step involves reacting the resultant 5-((tert-butoxycarbonyl)aminomethyl)-2-fluorobenzeneboronic acid of the first step with a 4-halo-pyridine such as 4-chloro-pyridine or 4-bromo-pyridine under Suzuki coupling conditions to yield (4-fluoro-3-pyridin-4-yl-benzyl)-carbamic acid tert-butyl ester. The third step involves employing selective hydrogenation conditions on the product of the second step to yield compound I. The invention is also directed to the intermediates 5-((tert-butoxycarbonyl)aminomethyl)-2-fluorobenzeneboronic acid (compound 11), and (4 fluoro-3-pyridin-4-yl-benzyl)-carbamic acid tert-butyl ester (compound 13).
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