Methyl 2-(2,6-difluorobenzyl)isonicotinate → Methyl 2-(2,6-difluorobenzyl)piperidine-4-carboxylate

HRID 1963314Notes

Reaction equation

HRID 1963314 reaction equation
[F:1][C:2]1[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[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]=[CH:17][CH:16]=[C:15]([F:19])[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 66731334Methyl 2-(2,6-difluorobenzyl)isonicotinate

Product 1

HCID 66731568Methyl 2-(2,6-difluorobenzyl)piperidine-4-carboxylateYield 97.4%

Reagents, catalysts & solvents 2

HCID 345198Adams' catalystCatalyst4×HCID 176Acetic AcidSolvent

Procedure

Methyl 2-(2,6-difluorobenzyl)isonicotinate (5.031 g, 19.11 mmol) was dissolved in acetic acid (49 mL) and platinum(IV) oxide (0.217 g, 0.96 mmol) was added. The mixture was hydrogenated in a Büchi hydrogenator at room temperature and 5 bar for 5 h. More platinum(IV) oxide (0.108 g, 0.48 mmol) was added and hydrogenation was continued for 1 h. Additional platinum(IV) oxide (0.108 g, 0.48 mmol) was added and the mixture was again hydrogenated for 1.5 h. More platinum(IV) oxide (0.108 g, 0.48 mmol) was added. After a total of 8.5 h the reaction mixture was filtered through celite and the catalyst was washed with MeOH. The eluate was concentrated and DCM and 1 M K2CO3 were added. The phases were separated and the organic phase was washed with brine before it was dried and concentrated to yield methyl 2-(2,6-difluorobenzyl)piperidine-4-carboxylate (5.01 g, 97%). MS m/z 270 (M+H)+

Workup

  1. customwas hydrogenated in a Büchi hydrogenator at room temperature
  2. waithydrogenation was continued for 1 h
  3. waitthe mixture was again hydrogenated for 1.5 h
  4. filtrationAfter a total of 8.5 h the reaction mixture was filtered through celite
  5. washthe catalyst was washed with MeOH
  6. concentrationThe eluate was concentrated
  7. additionDCM and 1 M K2CO3 were added
  8. customThe phases were separated
  9. washthe organic phase was washed with brine before it
  10. customwas dried
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-bdad237ada6d4898a0b3c04059cd9b6e
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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