Methyl 5-[4-(difluoromethoxy)phenyl]nicotinate → Methyl 5-[4-(difluoromethoxy)phenyl]piperidine-3-carboxylate

HRID 220032Notes

Reaction equation

HRID 220032 reaction equation
[F:1][CH:2]([F:20])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:11]=[N:12][CH:13]=[C:14]([CH:19]=2)[C:15]([O:17][CH3:18])=[O:16])=[CH:6][CH:5]=1>C(O)(=O)C.[Pd].[Pt](=O)=O>[F:20][CH:2]([F:1])[O:3][C:4]1[CH:5]=[CH:6][C:7]([CH:10]2[CH2:11][NH:12][CH2:13][CH:14]([C:15]([O:17][CH3:18])=[O:16])[CH2:19]2)=[CH:8][CH:9]=1

Participants

5

Reactant 1

HCID 58116524Methyl 5-[4-(difluoromethoxy)phenyl]nicotinate

Product 1

HCID 58116573Methyl 5-[4-(difluoromethoxy)phenyl]piperidine-3-carboxylate

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 345198Adams' catalystCatalystHCID 176Acetic AcidSolvent

Procedure

A solution of 8.6 g (30.9 mmol) of methyl 5-[4-(difluoromethoxy)phenyl]nicotinate in concentrated acetic acid (112 ml) was admixed with 841 mg of palladium/carbon (10% palladium) and 1.12 g of platinum(IV) oxide. This was followed by hydrogenation under a hydrogen atmosphere at standard pressure for 24 h. The reaction solution was concentrated under reduced pressure. The residue was taken up in water, acidified (pH 1) with 1 N hydrochloric acid, extracted with diethyl ether, then basified (pH>10) with saturated aqueous sodium hydrogencarbonate solution and extracted repeatedly with ethyl acetate. The combined filtrates were dried over sodium sulphate, filtered and concentrated under reduced pressure. Yield: 6.6 g (74% of theory)

Workup

  1. concentrationThe reaction solution was concentrated under reduced pressure
  2. extractionextracted with diethyl ether
  3. extractionextracted repeatedly with ethyl acetate
  4. dry with materialThe combined filtrates were dried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-bdef0b25777843a9a780fe8f7a560b79
Source dataset
uspto-grants-2012_06
Patent number
US08202862B2

Reaction notes

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