Piperidine → HCID 21129845, compound

HRID 1371231Notes

Reaction equation

HRID 1371231 reaction equation
[CH2:1]([C:5]1[O:13][C:12]2[C:7](=[N:8][C:9]([CH3:15])=[CH:10][C:11]=2Cl)[CH:6]=1)[CH2:2][CH2:3][CH3:4].[NH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1.C([O-])([O-])=O.[K+].[K+]>O>[CH2:1]([C:5]1[O:13][C:12]2[C:7](=[N:8][C:9]([CH3:15])=[CH:10][C:11]=2[N:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[CH:6]=1)[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 3

HCID 8082PiperidineHCID 11430Potassium CarbonateHCID 21129847HCID 21129847, compound

Product 1

HCID 21129845HCID 21129845, compoundYield 78.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of 2-butyl-7-chloro-5-methylfurano[3,2-b]pyridine (Example 229 (c)) (329 mg, 1.45 mmol) and piperidine (3 mL, 30.4 mmol) was added a mixture of K2CO3 (0.85 g, 5.8 mmol) in H2O (1 ML). Mixture stirred at 100° C. under N2 for 16 h. After cooling, the reaction mixture was concentrated. The residue was diluted with H2O (70 mL) and Et2O (50 mL). The mixture was transferred to a separatory funnel and the organic solution was collected. The aqueous solution was washed with Et2O (2×40 mL). The organic solutions were combined, washed with H2O (50 mL), saturated NaCl (70 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel with 50:50 EtOAc:hexanes as elutant to give 310 mg (77%) of 2-butyl-5-methyl-7-piperidylfurano[3,2-b]pyridine as a cream colored solid. This material (310 mg, 1.12 mmol) was dissolved in EtOAc (10 mL) and heated to boiling. To the hot solution was added 1M etheral HCl (1.20 mL, 1.20 mmol). The solution was left to cool to 25° C. The resulting solid was collected by filtration, washed with EtOAc (2×5 mL), Et2O (3×5 mL) and dried under vacuum at 25° C. to give 311 mg (69%) of the title compound as a white colored powder. Mp: 172-173° C. 1H NMR (CDCl3; 400 MHz): δ 0.95 (t, 3, J=7.4), 1.42 (hextet, 2, J=7.3), 1.69 (quintet, 2, J=7.7), 1.79 (br s, 6), 2.71 (s, 3), 2.79 (t, 2, J=7.5), 3.85 (br, 4), 6.29 (s, 1), 7.01 (s, 1), 15.56 (s, 1). MS m/z: 2793 (M+1 for free base). Anal. Calcd for C17H24N2O.HCl.0.5H2O: C, 64.24; H, 8.25; N, 8.82; Cl, 11.15. Found C, 64.42; H, 8.23; N, 8.75; Cl, 11.26.

Workup

  1. additionwas added
  2. temperatureAfter cooling
  3. concentrationthe reaction mixture was concentrated
  4. additionThe residue was diluted with H2O (70 mL) and Et2O (50 mL)
  5. customThe mixture was transferred to a separatory funnel
  6. customthe organic solution was collected
  7. washThe aqueous solution was washed with Et2O (2×40 mL)
  8. washwashed with H2O (50 mL), saturated NaCl (70 mL)
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by flash chromatography on silica gel with 50:50 EtOAc

Sources & evidence

ORD record
ord-3a35df70d8d9468997c6bb93d062f142
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

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