1-[[4-(trifluoromethyl)phenyl]methyl]piperazine

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared from 2-(4-(adamantan-1-yl)phenoxy)acetic acid (0.3 g, 1.04 mmol) and 1-(4-(trifluoromethyl)benzyl)piperazine (0.255 g, 1.04 mmol) according to the example 1, which was given 2-(4-(adamantan-1-yl)phenoxy)-1-(4-(4-(trifluoromethyl)benzyl)piperazin-1-yl) ethanone as a white solid (0.501 g, 93.3% yield).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1-(4-(trifluoromethyl)benzyl)piperazine (0.046 g, 0.188 mmol), 2-(2-oxo-3,3-diphenylpiperidin-1-yl)acetic acid (Example 68E, 0.053 g, 0.171 mmol) and N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (0.049 g, 0.257 mmol) in dichloromethane (0.5 mL) was stirred at room temperature. After stirring overnight, the reaction was loaded directly onto a SF15-12 silica gel column (Analogix®, Burlington, Wis.), and the title compound was eluted using a gradient of 0.4% to 4.5% methanol/dichloromethane over 20 minutes (flow=30 mL/minute). 1H NMR (300 MHz, CDCl3) δ ppm 7.56-7.60 (m, 2H), 7.42-7.46 (m, 2H), 7.27-7.33 (m, 8H), 7.18-7.25 (m, 2H), 4.23 (s, 2H), 3.66 (t, J=4.7 Hz, 2H), 3.55 (s, 2H), 3.50 (t, J=6.5 Hz, 2H), 3.44-3.49 (m, 2H), 2.62-2.66 (m, 2H), 2.35-2.50 (m, 4H), 1.79-1.88 (m, 2H); MS (ESI+) m/z 536 (M+H)+. the title compound was eluted over 20 minutes

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Synthesized according to General Procedure A: 4-trifluoromethylbenzyl chloride (4{15}, 5 g, 25.7 mmol, 1 equiv.), piperazine (13.3 g, 154.2 mmol, 6 equiv.), THF (56.1 mL). Purification with flash column chromatography on silica gel (4:1 EtOAc:MeOH) afforded 5{15} (3.97 g, 67%) as a light yellow liquid. 1H-NMR (400 MHz, CDCl3): δ 7.52 (d, 2H, J=8.0 Hz), 7.40 (d, 2H, J=8.0 Hz), 3.48 (s, 2H), 2.84 (t, 4H, J=4.8 Hz), 2.36 (br s, 4H), 1.55 (br s, 1H). 13C-NMR (100 MHz, CDCl3): δ 142.4, 129.1 (q, JC-F=32.1 Jz) 129.1 (br), 125.0 (br), 124.1 (q, JC-F=338.0 Hz), 62.9, 54.4, 45.9. 19F-NMR (375 MHz, CDCl3): δ-62.5. Synthesized Purification with flash column chromatography on silica gel (4:1 EtOAc:MeOH) afforded 5{15} (3.97 g, 67%) as a light yellow liquid

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared from 2-(4-(adamantan-1-yl)phenoxy)acetic acid (0.3 g, 1.04 mmol) and 1-(4-(trifluoromethyl)benzyl)piperazine (0.255 g, 1.04 mmol) according to the example 1, which was given 2-(4-(adamantan-1-yl)phenoxy)-1-(4-(4-(trifluoromethyl)benzyl)piperazin-1-yl) ethanone as a white solid (0.501 g, 93.3% yield).