Reaction SMILES: [CH3:1][C@H:2]1[CH2:7][NH:6][C@H:5]([CH3:8])[CH2:4][N:3]1[C@H:9]([C:24]1[CH:36]=[CH:35][C:27]([C:28]([N:30]([CH2:33][CH3:34])[CH2:31][CH3:32])=[O:29])=[CH:26][CH:25]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([O:16][S:17]([C:20]([F:23])([F:22])[F:21])(=[O:19])=[O:18])[CH:11]=1.[I-].[Na+].[CH2:39](N(CC)CC)C.[C:46]([O:54][CH2:55]Br)(=[O:53])[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1>C(#N)C>[CH2:31]([N:30]([CH2:33][CH3:34])[C:28]([C:27]1[CH:26]=[CH:25][C:24]([C@H:9]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([O:16][S:17]([C:20]([F:21])([F:22])[F:23])(=[O:18])=[O:19])[CH:11]=2)[N:3]2[C@@H:2]([CH3:1])[CH2:7][N:6]([CH2:39][C:50]3[CH:51]=[CH:52][C:47]([C:46]([O:54][CH3:55])=[O:53])=[CH:48][CH:49]=3)[C@H:5]([CH3:8])[CH2:4]2)=[CH:36][CH:35]=1)=[O:29])[CH3:32]
Reactant: CCN(CC)CC
Reactant: O=C(OCBr)c1ccccc1
Reactant: CCN(CC)C(=O)c1ccc([C@H](c2cccc(OS(=O)(=O)C(F)(F)F)c2)N2C[C@@H](C)NC[C@@H]2C)cc1
Agent: [I-]
Agent: [Na+]
Solvent: CC#N
Product: CCN(CC)C(=O)c1ccc([C@H](c2cccc(OS(=O)(=O)C(F)(F)F)c2)N2C[C@@H](C)N(Cc3ccc(C(=O)OC)cc3)C[C@@H]2C)cc1
Temperature: 25 °C
Reaction time: 120 h

Procedure:
4-((alpha-R)-alpha-((2S,5R)-2,5-Dimethyl-1-piperazinyl)-3-trifluoromethylsulfonyloxy-benzyl)-N,N-diethylbenzamide (Example 10, 844 mg, 1.6 mmol) in acetonitrile (8 mL) was added to sodium iodide (45 mg, 0.3 mmol) and stirred during the addition of triethylamine (1.0 mL, 726 mg, 7.17 mol), followed by methyl 4-(bromomethyl benzoate (916.3 mg, 4.0 mmol). The reaction mixture was sealed under nitrogen and stirred at ambient temperature for 5 days. The solvent was removed by evaporation and the residue was partitioned between ethyl acetate (10 mL) and saturated aqueous sodium bicarbonate solution (3 mL). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (3×10 mL). The combined organic extracts were dried over anhydrous sodium sulfate and evaporated to dryness. The residue was dissolved in ethyl acetate (5 mL) and applied to an intermediate (4×15 cm) Biotage silica column and eluted with ethyl acetate. Fractions containing the product, as evidenced by t.l.c. (silica, EM60F254, 100% EtOAc, Rf=0.74) were evaporated to dryness and dried at room temperature and 2 mm Hg to yield methyl 4-{(2R,5S)-4-[(R)-(4-diethylcarbamoylphenyl)(3-(trifluoromethylsulfonyloxy) phenyl)methyl]-2,5-dimethylpiperazin-1-ylmethyl}benzoate as a rigid white foam. The solid (1.09 g, 1.615 mmol) was dissolved in ethanol (10 mL) and sodium hydroxide solution (2.5 M, 6.46 mL, 16.16 mmol) was added in approximately 1 mL aliquots. The slightly turbid reaction mixture clarified about 5 min after the last addition to yield a yellow solution which was stirred for 16 h at ambient temperature. The solution was diluted with an equal volume of water and the ethanol was removed by evaporation along with an estimated 50% of the aqueous volume. The pH of the solution was adjusted to 4 with 3 M hydrochloric acid, to yield a flocculent white solid, which was collected by filtration and washed sparingly with cold water. After removal of granular solid from the filter, the remaining small amount of gummy material was removed from the filter, sonicated with water (˜1 mL) to yield a fine solid that was collected by filtration. After drying at room temperature and 5 mm Hg, both samples were shown to be identical by HPLC (Zorbax C-8, isocratic 40% 0.01 M NH4OAc in MeOH, 3 min: gradient to 100% MeOH, 45 min: isocratic MeOH 5 min. 1.0 mL/min: λobs=210 nm, Rt=10.58 min) and combined to yield the title compound (888 mg, 85.9% from 4-((alpha-R)-alpha-((2S,5R)-2,5-dimethyl-1-piperazinyl)-3-trifluoromethylsulfonyl oxybenzyl)-N,N-diethylbenzamide). Calc. for C32H39N3O4 1.5 NaCl 1.6 H2O:C, 59.48; H, 6.58; N, 6.50. Found C, 59.50; H, 6.45; N, 6.32% 1H NMR ((CD3)2SO+20% v/v 1-M NaOD in D2O, 300 MHz); δ 0.93 (d, J=6.0 Hz, 3H); 0.98 (d, J=5.9 Hz, 3H; both doublets overlapping br m, 6H); 1.9 (m, 2H); 2.54 (m, 2H, partially obscured by DMSO); 3.13 (br m, 2H); 3.22 (d, J=14.2 Hz, 1H); 3.34 (br m, 2H); 3.71 (d, J=14.0 Hz, 1H); 4.66 (s, 1H); 5.97 (d, J=6.9 Hz, 1H); 6.16 (d, J=7.9, 1H); 6.23 (s, 1H); 6.72 (t, J=7.7 Hz, 1H); 7.16 (d, J=7.8 Hz, 4H); 7.38 (d, J=8.1 Hz, 2H); 7.72 (d, J=8.1 Hz, 2H). Mass spectrum: (ESI−, DP-120V, MeOH); m/z: 529.0, (M+, 100%); 528, ((M−1)+, 57%); 512.6, ((M−17)+, 95%).