HCID 66732390, compound → HCID 66732167, compound

HRID 1963134Notes

Reaction equation

HRID 1963134 reaction equation
Cl.[F:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[C:11]([CH:16]=[CH:17][N:18]=2)[C:12]([O:14][CH3:15])=[O:13])=[CH:5][CH:4]=1>CO.[Pt](=O)=O>[F:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:10][CH:11]([C:12]([O:14][CH3:15])=[O:13])[CH2:16][CH2:17][NH:18]2)=[CH:5][CH:4]=1

Participants

4

Reactant 1

HCID 66732390HCID 66732390, compound

Product 1

HCID 66732167HCID 66732167, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 345198Adams' catalystCatalystHCID 887MethanolSolvent

Procedure

Methyl 2-(4-fluorophenyl)isonicotinate hydrochloride (6.4 g, 23.91 mmol) was dissolved in methanol (100 mL) and platinum(IV) oxide (0.271 g, 1.20 mmol) added. The resulting mixture was hydrogenated in a Büchi hydrogenator at room temperature and 5 bar for 21 h. The catalyst was filtered off, washed with MeOH and the filtrate evaporated. DCM and satd NaHCO3 were added and the phases separated. The organic layer was washed with brine, passed through a phase separator and evaporated to yield a brown oil. The residue was purified by automated flash chromatography on a Biotage® KP-SIL 100 g column. A gradient from 0% to 5% of MeOH in DCM (containing 1% Et3N) over 10 CV was used as mobile phase and then isocratically eluted with 5% of MeOH in DCM (containing 1% Et3N). Methyl 2-(4-fluorophenyl)piperidine-4-carboxylate (4.2 g, 74%) was isolated. MS m/z 238 (M+H)+

Workup

  1. customwas hydrogenated in a Büchi hydrogenator at room temperature
  2. filtrationThe catalyst was filtered off
  3. washwashed with MeOH
  4. customthe filtrate evaporated
  5. additionDCM and satd NaHCO3 were added
  6. customthe phases separated
  7. washThe organic layer was washed with brine
  8. customevaporated
  9. customto yield a brown oil
  10. customThe residue was purified by automated flash chromatography on a Biotage® KP-SIL 100 g column
  11. washisocratically eluted with 5% of MeOH in DCM (containing 1% Et3N)

Sources & evidence

ORD record
ord-1a03b9ef17d04e3eac65464951317fbf
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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