Pyridine → 1-Benzyl-4-[4-(5-cyclobutyl-[1,3,4]oxadiazol-2-yl)-phenyl]-4-(3-methoxy-phenyl)-piperidine

HRID 2085465Notes

Reaction equation

HRID 2085465 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([C:22]2[CH:37]=[CH:36][C:25]([C:26]([NH:28][NH:29][C:30]([CH:32]3[CH2:35][CH2:34][CH2:33]3)=O)=[O:27])=[CH:24][CH:23]=2)([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[CH:15]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CC=CC=1.S(OS(C(F)(F)F)(=O)=O)(C(F)(F)F)(=O)=O>C(Cl)Cl>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([C:22]2[CH:23]=[CH:24][C:25]([C:26]3[O:27][C:30]([CH:32]4[CH2:33][CH2:34][CH2:35]4)=[N:29][N:28]=3)=[CH:36][CH:37]=2)([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[CH:15]=2)[CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 67749Trifluoromethanesulfonic anhydrideHCID 44215095cyclobutanecarboxylic acid N'-{4-[1-benzyl-4-(3-methoxy-phenyl)-piperidin-4-yl]-benzoyl}hydrazide

Product 1

HCID 227298951-Benzyl-4-[4-(5-cyclobutyl-[1,3,4]oxadiazol-2-yl)-phenyl]-4-(3-methoxy-phenyl)-piperidineYield 99%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of cyclobutanecarboxylic acid N′-{4-[1-benzyl-4-(3-methoxy-phenyl)-piperidin-4-yl]-benzoyl}-hydrazide (0.2 g, 0.40 mmol) in CH2Cl2 (3 mL) was added pyridine (0.08 mL, 1.0 mmol). The reaction mixture was cooled to −78° C. Triflic anhydride (0.14 mL, 0.84 mmol) was added dropwise. The mixture was stirred at −78° C. for 1 hour and at room temperature for 2 hours. The reaction was quenched with saturated aqueous sodium bicarbonate (3 mL). The aqueous layer was washed with CH2Cl2 (3×5 mL) and the combined extracts were dried (MgSO4) and concentrated. Purification by flash chromatograpy with EtOAc afforded 0.19 g (quantitative yield) of 1-Benzyl-4-[4-(5-cyclobutyl-[1,3,4]oxadiazol-2-yl)-phenyl]-4-(3-methoxy-phenyl)-piperidine. 1HNMR (400 MHz, CDCl3) δ 7.92 (d, 2H), 7.37 (d, 2H), 7.36-7.16 (comp, 6H), 6.83 (d, 1H), 6.80 (s, 1H), 6.60 (d, 1H), 3.81-3.78 (m, 1H), 3.77 (s, 3H), 3.45 (s, 2H), 2.82-2.38 (comp, 10H), 2.21-2.19 (comp, 2H); MS (M+1) 480.2.

Workup

  1. customThe reaction was quenched with saturated aqueous sodium bicarbonate (3 mL)
  2. washThe aqueous layer was washed with CH2Cl2 (3×5 mL)
  3. dry with materialthe combined extracts were dried (MgSO4)
  4. concentrationconcentrated
  5. customPurification by flash chromatograpy with EtOAc

Sources & evidence

ORD record
ord-9e4d027f3a92459a9e899cef48e6b61e
Source dataset
uspto-grants-2004_04
Patent number
US06720336B2

Reaction notes

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