Reaction SMILES: [OH-].[NH4+:2].[CH:3]1([CH2:6][N:7]2[C:11]3[CH:12]=[CH:13][C:14](C(F)(F)F)=[CH:15][C:10]=3[N:9]=[C:8]2[CH2:20][O:21][CH2:22][C:23]2([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]2)[CH2:5][CH2:4]1>C(OCC)(=O)C>[C:23]([C:36]1[CH:41]=[CH:40][C:39]([C:13]2[CH:14]=[CH:15][C:10]3[N:9]=[C:8]([CH2:20][O:21][CH2:22][C:23]4([C:36]5[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=5)[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:33])[CH3:34])=[O:30])[CH2:25][CH2:24]4)[N:7]([CH2:6][CH:3]4[CH2:4][CH2:5]4)[C:11]=3[CH:12]=2)=[CH:38][CH:37]=1)#[N:2]
Reactant: CC(C)(C)OC(=O)N1CCC(COCc2nc3cc(C(F)(F)F)ccc3n2CC2CC2)(c2ccccc2)CC1
Reactant: [NH4+]
Agent: [OH-]
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)N1CCC(COCc2nc3ccc(-c4ccc(C#N)cc4)cc3n2CC2CC2)(c2ccccc2)CC1

Procedure:
tert-Butyl 4-(((1-(cyclopropylmethyl)-5-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate and tert-Butyl 4-(((1-(cyclopropylmethyl)-6-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate. 5-(Trifluoromethyl)-1H-benzo[d]imidazol-2-yl)methanol (665 mg, 1.77 mmol as TFA salt) was alkylated cyclopropylmethyl bromide following the procedure described for the synthesis of 5-Bromo-1-(cyclopropylmethyl)-1H-benzo[d]imidazol-2-yl)methanol and 6-bromo-1-(cyclopropylmethyl)-1H-benzo[d]imidazol-2-yl)methanol. After work up the crude product obtained was subjected to alkylation reaction with tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate as described in the synthesis of tert-butyl 4-(((5-bromo-1-(cyclopropylmethyl)-1H-benzo[d]imidazol-2-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate and tert-butyl 4-(((6-bromo-1-(cyclopropylmethyl)-1H-benzo[d]imidazol-2-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate. The crude product obtained was purified silica gel chromatography using a step gradient of ethyl acetate in hexane from 10% to 100%. After pooling and evaporating the fractions three major fractions were obtained. Fraction 1 (204 mg, tert-butyl 4-(((1-(cyclopropylmethyl)-5-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate containing phenylpiperidinyl alcohol as contaminant), Fraction 2 (513 mg, mixture of tert-butyl 4-(((1-(cyclopropylmethyl)-5-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate and tert-butyl 4-(((1-(cyclopropylmethyl)-6-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate and fraction 3 (tert-butyl 4-(((1-(cyclopropylmethyl)-6-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate containing more polar impurities). Fraction 1 was purified further by preparative HPLC (HPLC method 11) and tert-butyl 4-(((1-(cyclopropylmethyl)-5-(trifluoromethyl)-1 H-benzo [d]imidazol-2-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate (190 mg ) was isolated as free base after extractive work up using ethyl acetate and aqueous ammonium hydroxide as described in the synthesis of 5. tert-Butyl 4-(((1-(cyclopropylmethyl)-5-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate: 1H NMR (500 MHz, CD3OD) δ 7.93 (s, 1 H), 7.69 (d, J=8.5 Hz, 1 H), 7.62-7.58 (m, 1 H), 7.38-7.34 (m, 2 H), 7.30 (m, 2 H), 7.20 (m, 1 H), 4.73 (s, 2 H), 3.83 (d, J=7.0 Hz, 2 H), 3.73 (m, 2 H), 3.59 (s, 2 H), 3.05 (m, 2 H), 2.20 (m, 2 H), 1.84 (m, 2 H), 1.45 (s, 9 H), 1.04 (m, 1 H), 0.52-0.46 (m, 2 H), 0.35-0.29 (m, 2 H). 19F NMR (471 MHz, CD3OD) δ −68.9, −84.5.