Hydrochloric Acid → 2-(3,3-Difluoro-3-(4-fluorophenyl)propylthio)-nicotinic acid

HRID 1925557Notes

Reaction equation

HRID 1925557 reaction equation
Br[CH2:2][CH2:3][C:4]([C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=1)([F:6])[F:5].C([O-])([O-])=O.[K+].[K+].[SH:20][C:21]1[N:29]=[CH:28][CH:27]=[CH:26][C:22]=1[C:23]([OH:25])=[O:24].Cl>CN(C=O)C.CCCCCC.CC(=O)OCC.O>[F:5][C:4]([F:6])([C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=1)[CH2:3][CH2:2][S:20][C:21]1[N:29]=[CH:28][CH:27]=[CH:26][C:22]=1[C:23]([OH:25])=[O:24]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 671338221-(3-Bromo-1,1-difluoropropyl)-4-fluorobenzeneHCID 178524460HCID 178524460, compound

Product 1

HCID 671336742-(3,3-Difluoro-3-(4-fluorophenyl)propylthio)-nicotinic acidYield 31%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
90 °C

Procedure

1.02 g (4.0 mmol) of 1-(3-bromo-1,1-difluoropropyl)-4-fluorobenzene (precursor VC005) and 1.67 g (12.0 mmol) of K2CO3 were added to a solution of 620 mg (4.0 mmol) of 2-mercapto-nicotinic acid in DMF (10 ml), and the mixture was heated for 2 h at 90° C. Dilution with water (20 ml) was then carried out, and the pH was adjusted to −2 with 6M hydrochloric acid. Extraction with EA (3×40 ml) was then carried out. The combined organic phases were washed with water and brine, dried over Na2SO4, filtered and concentrated in vacuo. CC (hexane/EA 1:4) of the residue yielded 400 mg (1.2 mmol, 31%) of 2-(3,3-difluoro-3-(4-fluorophenyl)propylthio)-nicotinic acid.

Workup

  1. extractionExtraction with EA (3×40 ml)
  2. washThe combined organic phases were washed with water and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-911744400e8541d399fa041ec0d9d740
Source dataset
uspto-grants-2012_05
Patent number
US08178684B2

Reaction notes

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