Methyl 2-(3,4-difluorobenzyl)isonicotinate → Methyl 2-(3,4-difluorobenzyl)piperidine-4-carboxylate

HRID 1963306Notes

Reaction equation

HRID 1963306 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=1[F:19])[CH2:5][C:6]1[CH:7]=[C:8]([CH:13]=[CH:14][N:15]=1)[C:9]([O:11][CH3:12])=[O:10]>C(O)(=O)C.[Pt](=O)=O>[F:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=1[F:19])[CH2:5][CH:6]1[CH2:7][CH:8]([C:9]([O:11][CH3:12])=[O:10])[CH2:13][CH2:14][NH:15]1

Participants

4

Reactant 1

HCID 66732424Methyl 2-(3,4-difluorobenzyl)isonicotinate

Product 1

HCID 66731879Methyl 2-(3,4-difluorobenzyl)piperidine-4-carboxylateYield 103.3%

Reagents, catalysts & solvents 2

HCID 345198Adams' catalystCatalyst3×HCID 176Acetic AcidSolvent

Procedure

Methyl 2-(3,4-difluorobenzyl)isonicotinate (7.7 g, 29.25 mmol) was dissolved in acetic acid (75 mL) and platinum(IV) oxide (0.332 g, 1.46 mmol) added. The resulting mixture was hydrogenated in a Büchi hydrogenator at room temperature and 5 bar for 4 h 45 min. More platinum(IV) oxide (0.166 g, 0.73 mmol) was added and the hydrogenation continued at 5 bar for 2 h. More platinum(IV) oxide (0.166 g, 0.73 mmol) was added and the hydrogenation continued at 5 bar for 1 h 20 min. The catalyst was filtered off and washed with MeOH and the eluate evaporated. DCM and 10% K2CO3 were added and the phases separated. The organic layer was washed with brine, passed through a phase separator and evaporated to yield crude methyl 2-(3,4-difluorobenzyl)piperidine-4-carboxylate (8.133 g, 103%) as a brown oil. MS m/z 270 (M+H)+

Workup

  1. customwas hydrogenated in a Büchi hydrogenator at room temperature
  2. waitthe hydrogenation continued at 5 bar for 2 h
  3. waitthe hydrogenation continued at 5 bar for 1 h 20 min
  4. filtrationThe catalyst was filtered off
  5. washwashed with MeOH
  6. additionDCM and 10% K2CO3 were added
  7. customthe phases separated
  8. washThe organic layer was washed with brine
  9. customevaporated

Sources & evidence

ORD record
ord-2a7f7186fe964cf7b0313d9a39378a36
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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