n-(Tert-butoxycarbonyl)-3-[4-(2-pyridyl)-piperidin-1-yl]propylamine → 4-(2-pyridinyl)-1-Piperidinepropanamine

HRID 2086908Notes

Reaction equation

HRID 2086908 reaction equation
C(OC([NH:8][CH2:9][CH2:10][CH2:11][N:12]1[CH2:17][CH2:16][CH:15]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=2)[CH2:14][CH2:13]1)=O)(C)(C)C>ClCCl.FC(F)(F)C(O)=O>[N:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[CH:15]1[CH2:14][CH2:13][N:12]([CH2:11][CH2:10][CH2:9][NH2:8])[CH2:17][CH2:16]1

Participants

4

Reactant 1

HCID 22725173n-(Tert-butoxycarbonyl)-3-[4-(2-pyridyl)-piperidin-1-yl]propylamine

Product 1

HCID 101768154-(2-pyridinyl)-1-PiperidinepropanamineYield 100%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

3-[4-(2-Pyridyl)-piperidine-1-yl]propylamine (Scheme 6). To 1-Benzyl-4-(2-pyridyl)-piperidine (3.26 g, 12.9 mmol) in dry methanol (25 ml), 10, palladium hydroxide (1.9 g) was added and the solution was hydrogenated at 200 psi for 24 hours. The solution was filtered over celite, concentrated to give 2.1 g (99%) of 4-(2-pyridyl)-piperidine which was used as such for the subsequent step. A mixture of 3-bromopropylamine hydrobromide (20 g, 91.3 mmol), potassium carbonate (37.85 g, 273.9 mmol) and di-tert-butyldicarbonate (21.90 g, 100 mmol) in methanol was stirred at room temperature for 24 hours. The reaction mixture was concentrated and partitioned between 250 ml EtOAc and 50 ml water, dried over sodium sulfate, filtered and concentrated. Purification of the crude product by column chromatography (Hexane: EtOAc, 4.5:0.5) gave 17.5 g (80%) of the product as a pale yellow oil. To a stirred solution of the 4-(2-pyridyl)-piperidine (1.86 g, 11.4 mmol) in dioxane (20 ml), N-(tert-butoxycarbonyl)-3-bromopropylamine (2.82 g, 11.4 mmol) and potassium carbonate (3.16 g, 22.9 mmol) were added and the solution refluxed for 24 hours. The reaction mixture was cooled to room temperature, concentrated and partitioned between 40 ml chloroform and 5 ml water. The organic layer was dried over sodium sulfate, filtered and concentrated. The crude product was purified by column chromatography (ethyl acetate:methanol, 4:1) to yield 1.86 g (49%) of the required product as a colorless oil; 1H-NMR (CDCl3): δ 1.45 (s, 9H), 1.54-1.69 (m, 8H), 2.21-2.68 (m, 2H), 2.74-2.80 (m, 1H), 3.02-3.22 (m, 4H), 5.41 (s, 1H), 7.13-7.17 (m, 1H), 7.33 (d, J=7.93 Hz, 1H).7.63 (t, J=7.6 Hz, 1H), 8.54 (d, J=4.6 Hz, 1H). To N-(tert-butoxycarbonyl)-3-[4-(2-pyridyl)-piperidin-1-yl]propylamine (0.15 g, 0.45 mmol) in 5 ml of dichloromethane, 1 ml of trifluoroacetic acid was added and the solution stirred at room temperature for 1 hour. The solution was concentrated, neutralized with 10% KOH solution and extracted into 25 ml of dichloromethane. The organic layer was dried over sodium sulfate, filtered and concentrated to give 0.098 g (100%) of 3-[4-(2-pyridyl)-piperidin-1-yl]propylamine which was used as such for the subsequent step (step h).

Workup

  1. concentrationThe solution was concentrated
  2. extractionextracted into 25 ml of dichloromethane
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-c768b3a1c8d34e3ab42a00af0ceef351
Source dataset
uspto-grants-2004_04
Patent number
US06727257B1

Reaction notes

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