N-methyl-2-pyrrolidone → 1,1-Dimethylethyl 4-[(6-pentyl-8-quinolinyl)oxy]-1-piperidinecarboxylate

HRID 1363005Notes

Reaction equation

HRID 1363005 reaction equation
Cl[C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([O:12][CH:13]3[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]3)[CH:11]=1)[N:8]=[CH:7][CH:6]=[CH:5]2.CN1C(=O)CCC1.[CH2:33]([Mg]Br)[CH2:34][CH2:35][CH2:36][CH3:37].[Cl-].[NH4+]>C1COCC1.C/C(/O)=C/C(C)=O.C/C(/O)=C/C(C)=O.C/C(/O)=C/C(C)=O.[Fe]>[CH2:33]([C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([O:12][CH:13]3[CH2:14][CH2:15][N:16]([C:19]([O:21][C:22]([CH3:24])([CH3:25])[CH3:23])=[O:20])[CH2:17][CH2:18]3)[CH:11]=1)[N:8]=[CH:7][CH:6]=[CH:5]2)[CH2:34][CH2:35][CH2:36][CH3:37]

Participants

7

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 25517Ammonium ChlorideHCID 669219581,1-Dimethylethyl 4-[(6-chloro-8-quinolinyl)oxy]-1-piperidinecarboxylate2×HCID 178445865HCID 178445865, compound

Product 1

HCID 669215051,1-Dimethylethyl 4-[(6-pentyl-8-quinolinyl)oxy]-1-piperidinecarboxylateYield 74%

Reagents, catalysts & solvents 2

HCID 11110968Iron (III) acetylacetonateCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

1,1-Dimethylethyl 4-[(6-chloro-8-quinolinyl)oxy]-1-piperidinecarboxylate (for example, as prepared for Intermediate 6) (2.73 g, 7.5 mmol) was dissolved in a mixture of THF (55 ml), NMP (5.6 ml) and iron (III) acetylacetonate (220 mg, 0.62 mmol) were added, and the mixture was cooled to 0° C. and stirred under a nitrogen atmosphere. n-Pentyl magnesium bromide (commercially available, for example, from TCI-Europe and/or Aldrich) was added dropwise over 9 min. The stirring was continued at 0° C. for 1 h, and the reaction was then allowed to warm to room temperature with stirring overnight. The reaction mixture was treated with aqueous ammonium chloride solution and extracted with EtOAc (×3). The combined organic extracts were filtered, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica chromatography (2×100 g), eluting with 0-50% EtOAc-cyclohexane over 40 min. The relevant fractions were concentrated in vacuo to give the title compound as a yellow oil (2.2 g, 74%): LCMS RT=3.76 min, ES+ve m/z 399 [M+H]+.

Workup

  1. additionwere added
  2. customwas added dropwise over 9 min
  3. temperatureto warm to room temperature
  4. stirringwith stirring overnight
  5. extractionextracted with EtOAc (×3)
  6. filtrationThe combined organic extracts were filtered
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by silica chromatography (2×100 g)
  10. washeluting with 0-50% EtOAc-cyclohexane over 40 min
  11. concentrationThe relevant fractions were concentrated in vacuo

Sources & evidence

ORD record
ord-7f451ae0c3dd4cadab5a2178d68ced1a
Source dataset
uspto-grants-2011_02
Patent number
US07884114B2

Reaction notes

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