Methyl 2-(2,4-difluorobenzyl)isonicotinate → Methyl 2-(2,4-difluorobenzyl)piperidine-4-carboxylate

HRID 1963322Notes

Reaction equation

HRID 1963322 reaction equation
[F:1][C:2]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:3]=1[CH2:4][C:5]1[CH:6]=[C:7]([CH:12]=[CH:13][N:14]=1)[C:8]([O:10][CH3:11])=[O:9]>C(O)(=O)C.[Pt](=O)=O>[F:1][C:2]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:3]=1[CH2:4][CH:5]1[CH2:6][CH:7]([C:8]([O:10][CH3:11])=[O:9])[CH2:12][CH2:13][NH:14]1

Participants

4

Reactant 1

HCID 66731542Methyl 2-(2,4-difluorobenzyl)isonicotinate

Product 1

HCID 66731679Methyl 2-(2,4-difluorobenzyl)piperidine-4-carboxylateYield 99.1%

Reagents, catalysts & solvents 2

HCID 345198Adams' catalystCatalyst3×HCID 176Acetic AcidSolvent

Procedure

Methyl 2-(2,4-difluorobenzyl)isonicotinate (7.011 g, 26.63 mmol) was dissolved in acetic acid (50 mL) and platinum(IV) oxide (0.302 g, 1.33 mmol) added. The resulting mixture was hydrogenated in a Büchi hydrogenator for 4.5 h at room temperature and 5 bar. platinum(IV) oxide (174 mg) was added and the hydrogenation continued at room temperature at 5 bar for 2 h. Additional platinum(IV) oxide (185 mg) was added and the hydrogenation continued at room temperature at 5 bar for 2 h. The catalyst was filtered off and washed with MeOH and the eluate evaporated. DCM and 10% K2CO3 were added and the phases separated. The water phase was extracted with DCM and the combined organic phase washed with water, passed through a phase separator and evaporated to yield methyl 2-(2,4-difluorobenzyl)-piperidine-4-carboxylate (7.103 g, 99%) as a yellow oil. MS m/z 270 (M+H)+

Workup

  1. waitthe hydrogenation continued at room temperature at 5 bar for 2 h
  2. waitthe hydrogenation continued at room temperature at 5 bar for 2 h
  3. filtrationThe catalyst was filtered off
  4. washwashed with MeOH
  5. additionDCM and 10% K2CO3 were added
  6. customthe phases separated
  7. extractionThe water phase was extracted with DCM
  8. washthe combined organic phase washed with water
  9. customevaporated

Sources & evidence

ORD record
ord-50f38bd351bb41a5b5547f8741848292
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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