Hydrochloric Acid → Methyl 5-[3-fluoro-4-(2,2,2-trifluoroethyl)phenyl]piperidine-3-carboxylate

HRID 661248Notes

Reaction equation

HRID 661248 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:13]2[CH:14]=[N:15][CH:16]=[C:17]([CH:22]=2)[C:18]([O:20][CH3:21])=[O:19])[CH:5]=[CH:6][C:7]=1[CH2:8][C:9]([F:12])([F:11])[F:10].Cl>CO.[Pt](=O)=O>[F:1][C:2]1[CH:3]=[C:4]([CH:13]2[CH2:14][NH:15][CH2:16][CH:17]([C:18]([O:20][CH3:21])=[O:19])[CH2:22]2)[CH:5]=[CH:6][C:7]=1[CH2:8][C:9]([F:12])([F:10])[F:11]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 58116533Methyl 5-[3-fluoro-4-(2,2,2-trifluoroethyl)phenyl]nicotinate

Product 1

HCID 58116551Methyl 5-[3-fluoro-4-(2,2,2-trifluoroethyl)phenyl]piperidine-3-carboxylate

Reagents, catalysts & solvents 2

HCID 345198Adams' catalystCatalyst3×HCID 887MethanolSolvent

Procedure

A solution of 7.75 g (17.1 mmol, purity 69%) of the compound from Example 75A in methanol (107 ml) was admixed with 1.50 g of platinum(IV) oxide and concentrated hydrochloric acid solution (13.4 ml). This was followed by hydrogenation under a hydrogen atmosphere at 3.5 bar overnight, then addition of another 800 mg of platinum(IV) oxide and again by hydrogenation under a hydrogen atmosphere at 3.5 bar overnight. Addition of another 1.00 g of platinum(IV) oxide was followed by hydrogenation under a hydrogen atmosphere at 3.5 bar overnight. The reaction solution was filtered through Celite, the filter residue was washed with methanol and the combined filtrates were concentrated under reduced pressure. The residue was taken up in water, then adjusted to pH=9 with a 1 N aqueous sodium hydroxide solution and subsequently extracted with ethyl acetate. The organic phase was dried over sodium sulphate, filtered and concentrated under reduced pressure. Yield: 6.01 g (86% of theory, purity 78%)

Workup

  1. customThis was followed by hydrogenation under a hydrogen atmosphere at 3.5 bar overnight
  2. customat 3.5 bar overnight
  3. customwas followed by hydrogenation under a hydrogen atmosphere at 3.5 bar overnight
  4. filtrationThe reaction solution was filtered through Celite
  5. washthe filter residue was washed with methanol
  6. concentrationthe combined filtrates were concentrated under reduced pressure
  7. extractionsubsequently extracted with ethyl acetate
  8. dry with materialThe organic phase was dried over sodium sulphate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f15f722febf944cf8f68b89d2f84dc26
Source dataset
uspto-grants-2011_12
Patent number
US08084469B2

Reaction notes

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