CS(O[CH2:6][C:7]1[CH:16]=[CH:15][C:14]2[C@H:13]([NH:17]C(OC(C)(C)C)=O)[CH2:12][CH2:11][CH2:10][C:9]=2[CH:8]=1)(=O)=O.[F:25][CH:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1.Cl.C([O-])([O-])=O.[K+].[K+]>C1COCC1>[F:25][CH:26]1[CH2:31][CH2:30][N:29]([CH2:6][C:7]2[CH:8]=[C:9]3[C:14](=[CH:15][CH:16]=2)[C@H:13]([NH2:17])[CH2:12][CH2:11][CH2:10]3)[CH2:28][CH2:27]1
A mixture of (R)-(5-(tert-butoxycarbonylamino)-5,6,7,8-tetrahydronaphthalen-2-yl)methyl methanesulfonate (2.0 g, 5.633 mmol, 1.0 eq.), 4-fluoropiperidine.HCl (0.78 g, 5.633 mmol, 1.0 eq.) and K2CO3 (2.33 g, 16.9 mmol, 3.0 eq.) in THF (25 ml) was heated at reflux for 16 h. After completion of the reaction (monitored by TLC), the solvent was evaporated under reduced pressure and the residue was dissolved in ethyl acetate (150 ml), washed with water (100 ml) and brine (100 ml), and dried over Na2SO4. The solvent was evaporated under reduced pressure to give the crude product which was purified by column chromatography (silica gel; 40% ethyl acetate/hexanes) to yield the title compound as a light yellow solid. Yield: 60% (1.22 g, 3.37 mmol) 2. TFA (1 ml) was added to a solution of (R)-tert-butyl 6-((4-fluoropiperidin-1-yl)methyl)-1,2,3,4-tetrahydronaphthalen-1-ylcarbamate (325 mg, 0.898 mmol, 1.0 eq.) in DCM (4 ml) at 0° C. and the resulting reaction mixture was stirred at 25° C. for 4 h. The solvent was evaporated under reduced pressure and the residue was azeotroped with toluene to yield the desired product which was employed in the next step.
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