2,4,6-trifluorobenzonitrile

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

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

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

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

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A DMSO (25 mL, 0.1M) solution containing 4-N—BOC-aminopiperidine (500 mg, 2.5 mmol, 1.0 eq), 2,4,6-trifluorobenzonitrile (393 mg, 2.5 mmol, 1.0 eq), and potassium carbonate (691 mg, 5.0 mmol, 2.0 eq) was heated to 100° C. for 18 h. The resulting mixture was cooled to RT, poured in H2O (ca 50 mL), and extracted (3×) with EtOAc. The combined extracts were washed (2×) with H2O, dried over MgSO4, and concentrated in vacuo. The resulting solid was purified via flash chromatography using 1:1 hexanes/EtOAc as the mobile phase. Isolated 594 mg (1.76 mmol, 70% yield). The resulting mixture was cooled to RT extracted (3×) with EtOAc The combined extracts were washed (2×) with H2O dried over MgSO4 concentrated in vacuo The resulting solid was purified via flash chromatography Isolated 594 mg (1.76 mmol, 70% yield)

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: By an operation in the same manner as in Example 1 and using (2S,3S)-2,3-diethylpyrrolidin-3-ol 0.5 oxalate (197 mg), 2,4,6-trifluorobenzonitrile (295 mg) and lithium carbonate (192 mg), the title compound was obtained as a colorless solid (yield: 157 mg, yield: 54%).

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

Procedure: By an operation in the same manner as in Example 1 and using (2S,3S)-2,3-diethylpyrrolidin-3-ol 0.5 oxalate (197 mg), 2,4,6-trifluorobenzonitrile (295 mg) and lithium carbonate (192 mg), the title compound was obtained as a colorless solid (yield: 157 mg, yield: 54%).

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

Procedure: By an operation in the same manner as in Example 1 and using (2S,3S)-2-ethyl-3-methylpyrrolidin-3-ol 0.5 oxalate (200 mg), 2,4,6-trifluorobenzonitrile (270 mg) and lithium carbonate (187 mg), the title compound was obtained as a colorless solid (yield: 187.5 mg, yield: 61%).

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

Procedure: By an operation in the same manner as in Example 1 and using (2S,3R)-3-cyclopropyl-2-methylpyrrolidin-3-ol 0.5 oxalate (200 mg), 2,4,6-trifluorobenzonitrile (288 mg) and lithium carbonate (180 mg), the title compound was obtained as a colorless solid (yield: 172 mg, yield: 51%).

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

Procedure: By an operation in the same manner as in Example 1 and using (2S,3R)-3-cyclopropyl-2-isopropylpyrrolidin-3-ol 0.5 oxalate (215 mg), 2,4,6-trifluorobenzonitrile (157 mg) and lithium carbonate (163 mg), the title compound was obtained as a colorless solid (yield: 115 mg, yield: 38%).