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HCID 68559388, compound → 6-Difluoromethyl-2-(3-methoxy-propyl)-nicotinic acid methyl ester

HRID 19997
Notes
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Reaction equation

HRID 19997 reaction equation
[CH3:1][O:2][C:3](=[O:19])[C:4]1[CH:9]=[CH:8][C:7]([C:10](Cl)([F:12])[F:11])=[N:6][C:5]=1[CH2:14][CH2:15][CH2:16][O:17][CH3:18].[H][H]>CO.C(N(CC)CC)C.[Pd]>[CH3:1][O:2][C:3](=[O:19])[C:4]1[CH:9]=[CH:8][C:7]([CH:10]([F:11])[F:12])=[N:6][C:5]=1[CH2:14][CH2:15][CH2:16][O:17][CH3:18]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 2

HCID 68559388HCID 68559388, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 685607376-Difluoromethyl-2-(3-methoxy-propyl)-nicotinic acid methyl esterYield 113.4%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolvent
HCID 8471
Triethylamine
Solvent

Procedure

A solution of 194 g of 6-(Chloro-difluoro-methyl)-2-(3-methoxy-propyl)-nicotinic acid methyl ester (prepared according to WO 04/078729) in methanol (ca. 2 liter) and triethylamine (100 ml) is hydrogenated at 1 Atm hydrogen pressure in the presence of 2 g of 5% palladium supported on carbon. After completion of the reduction the reaction mixture is filtered through hyflo, and the filtrate diluted with water and the water/methanol mixture then extracted with ethyl acetate. The combined ethyl acetate extracts are washed with saturated aqueous sodium chloride solution, dried over magnesium sulphate and then concentrated in vacuo to give 194.2 g 6-Difluoromethyl-2-(3-methoxy-propyl)-nicotinic acid methyl ester as a pale coloured oil.

Workup

  1. filtrationAfter completion of the reduction the reaction mixture is filtered through hyflo
  2. additionthe filtrate diluted with water
  3. extractionthe water/methanol mixture then extracted with ethyl acetate
  4. washThe combined ethyl acetate extracts are washed with saturated aqueous sodium chloride solution
  5. dry with materialdried over magnesium sulphate
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-42fb344170e94a92985abc60d64e31f2
Source dataset
uspto-grants-2010_06
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07745495B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes