(3aR,4R,6aS)-1,2,3,3a,4,5,6,6a-octahydrocyclopenta[c]pyrrol-4-ol

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (3aR,4R,6aS)-Octahydrocyclopenta[c]pyrrol-4-ol (1.65 g, 12.97 mmol) from Example 29, 2-bromo-6-(trifluoromethyl)pyridine (3.66 g, 16.22 mmol) and triethylamine (7.23 mL, 51.9 mmol) were combined in ethanol (7.23 mL). The reaction was heated at 80° C. for 24 hours and the solvent was concentrated in vacuo. The resulting residue was purified by silica gel chromatography using 0-40% ethyl acetate/hexane as eluent to give the title compound and the title compound of Example 31: 1H NMR (500 MHz, pyridine-d5) δ ppm 7.47 (t, J=7.9, 1H), 6.94 (d, J=7.2, 1H), 6.53 (d, J=8.6, 1H), 6.38 (d, J=4.1, 1H), 4.47-4.38 (m, 1H), 4.12 (dd, J=11.0, 4.3, 1H), 3.70-3.63 (m, 1H), 3.53 (t, J=10.0, 1H), 3.38 (dd, J=10.4, 4.6, 1H), 2.80-2.73 (m, 1H), 2.72-2.64 (m, 1H), 1.97-1.74 (m, 3H), 1.64-1.56 (m, 1H); MS (ESI+) m/z 273 (M+H)+. the solvent was concentrated in vacuo The resulting residue was purified by silica gel chromatography

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (3aR,4R,6aS)-Octahydrocyclopenta[c]pyrrol-4-ol (1.65 g, 12.97 mmol) from Example 29, 2-bromo-6-(trifluoromethyl)pyridine (3.66 g, 16.22 mmol) and triethylamine (7.23 mL, 51.9 mmol) were combined in ethanol (7.23 mL). The reaction was heated at 80° C. for 24 hours and the solvent was concentrated in vacuo. The resulting residue was purified by silica gel chromatography using 0-40% ethyl acetate/hexane as eluent to give the title compound and the title compound of Example 31: 1H NMR (500 MHz, pyridine-d5) δ ppm 7.47 (t, J=7.9, 1H), 6.94 (d, J=7.2, 1H), 6.53 (d, J=8.6, 1H), 6.38 (d, J=4.1, 1H), 4.47-4.38 (m, 1H), 4.12 (dd, J=11.0, 4.3, 1H), 3.70-3.63 (m, 1H), 3.53 (t, J=10.0, 1H), 3.38 (dd, J=10.4, 4.6, 1H), 2.80-2.73 (m, 1H), 2.72-2.64 (m, 1H), 1.97-1.74 (m, 3H), 1.64-1.56 (m, 1H); MS (ESI+) m/z 273 (M+H)+. the solvent was concentrated in vacuo The resulting residue was purified by silica gel chromatography

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

Procedure: (3aR,4R,6aS)-2-Benzyloctahydrocyclopenta[c]pyrrol-4-ol (2.88 g, 13.25 mmol) from Example 28 and ethanol (40 mL) were added to 20% Pd(OH)2—C, wet (0.576 g, 4.10 mmol) in a 250 mL stainless steel pressure bottle and stirred for 2 hours at 30 psi hydrogen gas at 50° C. The mixture was filtered through a nylon membrane, and the solvent was removed in vacuo to give the title compound: 1H NMR (500 MHz, pyridine-d5) δ ppm 4.82 (s, 4H), 4.37 (dd, J=10.5, 4.8, 1H), 3.52 (dd, J=10.8, 1.7, 1H), 2.96-2.86 (m, 1H), 2.76 (dd, J=10.8, 6.9, 1H), 2.71 (dd, J=10.8, 1.8, 1H), 2.56-2.45 (m, 2H), 1.89 (td, J=11.7, 5.3, 1H), 1.80 (ddd, J=12.5, 10.3, 6.8, 1H), 1.66-1.58 (m, 1H), 1.50-1.42 (m, 1H); MS (ESI+) m/z 128 (M+H)+. The mixture was filtered through a nylon membrane the solvent was removed in vacuo

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

Procedure: (3aR,4R,6aS)-2-Benzyloctahydrocyclopenta[c]pyrrol-4-ol (2.88 g, 13.25 mmol) from Step 1 and ethanol (40 mL) were added to 20% Pd(OH)2—C, wet (0.576 g, 4.10 mmol) in a 250 mL stainless steel pressure bottle and stirred for 2 hours under 30 psi hydrogen gas at 50° C. The mixture was filtered through a nylon membrane and the solvent was removed in vacuo to give (3aR,4R,6aS)-octahydrocyclopenta[c]pyrrol-4-ol: 1H NMR (500 MHz, pyridine-d5) δ ppm 4.82 (s, 4H), 4.37 (dd, J=10.5, 4.8, 1H), 3.52 (dd, J=10.8, 1.7, 1H), 2.96-2.86 (m, 1H), 2.76 (dd, J=10.8, 6.9, 1H), 2.71 (dd, J=10.8, 1.8, 1H), 2.56-2.45 (m, 2H), 1.89 (td, J=11.7, 5.3, 1H), 1.80 (ddd, J=12.5, 10.3, 6.8, 1H), 1.66-1.58 (m, 1H), 1.50-1.42 (m, 1H); MS (ESI+) m/z 128 (M+H) The mixture was filtered through a nylon membrane the solvent was removed in vacuo