Ammonium Chloride → 1,1-Dimethylethyl 4-[(6-butyl-8-quinolinyl)oxy]-1-piperidinecarboxylate

HRID 1363001Notes

Reaction equation

HRID 1363001 reaction equation
[CH2:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13](F)[CH:14]=1)[N:11]=[CH:10][CH:9]=[CH:8]2)[CH2:2][CH2:3][CH3:4].[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][CH:26]([OH:29])[CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:18])[CH3:17].CC(C)([O-])C.[Na+].[Cl-].[NH4+]>CN1C(=O)CCC1>[CH2:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([O:29][CH:26]3[CH2:25][CH2:24][N:23]([C:21]([O:20][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:22])[CH2:28][CH2:27]3)[CH:14]=1)[N:11]=[CH:10][CH:9]=[CH:8]2)[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 23676156Sodium t-butoxideHCID 579260496-Butyl-8-fluoroquinoline2×

Product 1

HCID 579260451,1-Dimethylethyl 4-[(6-butyl-8-quinolinyl)oxy]-1-piperidinecarboxylate

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

A solution of 6-butyl-8-fluoroquinoline (for example, as prepared for Intermediate 2) (14.4 g, 70.9 mmol) in NMP (20 ml) was added to a mixture of tert-butyl-4-hydroxy-1-piperidinecarboxylate (commercially available, for example, from Aldrich) (21.6 g, 108 mmol) and sodium tert-butoxide (10.4 g, 108 mmol) in NMP (75 ml), and the resulting mixture was stirred at 140° C. for approximately 90 min and then allowed to cool overnight. The reaction mixture was treated with ammonium chloride solution and extracted with EtOAc (×2). The combined organic extracts were washed with water, dried (MgSO4), filtered and evaporated to dryness. The residue was purified by flash chromatography eluting with DCM-EtOAc (1:0 to 1:1) and then twice by Flashmaster chromatography eluting with DCM-EtOAc (1:0 to 3:1) over 40 min to give the title compound (22 g). LCMS RT=3.49 min, ES+ve m/z 385 [M+H]+

Workup

  1. temperatureto cool overnight
  2. extractionextracted with EtOAc (×2)
  3. washThe combined organic extracts were washed with water
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated to dryness
  7. customThe residue was purified by flash chromatography
  8. washeluting with DCM-EtOAc (1:0 to 1:1)
  9. washtwice by Flashmaster chromatography eluting with DCM-EtOAc (1:0 to 3:1) over 40 min

Sources & evidence

ORD record
ord-1fc7f3c054c74bffb881bbe71d2c184f
Source dataset
uspto-grants-2011_02
Patent number
US07884114B2

Reaction notes

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