Sodium Hydroxide → 6-(3-Fluoropropoxy)-3-pyridinecarboxylic acid

HRID 1099432Notes

Reaction equation

HRID 1099432 reaction equation
[H-].[Na+].[F:3][CH2:4][CH2:5][CH2:6][OH:7].Cl[C:9]1[CH:19]=[CH:18][C:12]([C:13]([O:15]CC)=[O:14])=[CH:11][N:10]=1.[OH-].[Na+]>CN(C)C=O.C(O)C>[F:3][CH2:4][CH2:5][CH2:6][O:7][C:9]1[CH:19]=[CH:18][C:12]([C:13]([OH:15])=[O:14])=[CH:11][N:10]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 680423-Fluoro-1-propanolHCID 2799611Ethyl 6-chloronicotinate

Product 1

HCID 251165286-(3-Fluoropropoxy)-3-pyridinecarboxylic acid

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride (0.220 g, 5.50 mmol) was added to a solution of 3-fluoropropan-1-ol (0.390 g, 5 mmol) in N,N-dimethylformamide (5 mL). The mixture was stirred under an atmosphere of nitrogen for 25 min and added a solution of ethyl 6-chloronicotinate (0.928 g, 5.00 mmol) in N,N-dimethylformamide (2.5 mL). The reaction mixture was stirred for 35 min and then quenched with water. The reaction mixture was extracted with ethyl acetate, the organic layer was washed with brine, dried over magnesium sulfate and evaporated in vacuo. Purification by column chromatography using a gradient of ethyl acetate in heptane yielded an oil. The crude was dissolved in 1M sodium hydroxide, (16.50 mL, 16.50 mmol) and ethanol (20 mL) and heated to 50° C. for 1.5 h. The organic solvent was removed in vacuo, and the residual aqueous solution was cooled on ice. 2 M hydrochloric acid was added until an acidic pH was reached. The obtained precipitate was filtered off, washed with ice-water, and dried in vacuo affording the title compound, 0.53 g (81%) as a white solid; 1H NMR (400 MHz, DMSO-d6) δ ppm 8.71 (dd, 1 H), 8.14 (dd, 1 H), 6.90 (dd, 1 H), 4.65 (t, 1 H), 4.54 (t, 1 H), 4.43 (t, 2 H), 2.05-2.19 (m, 2 H); MS (APPI/APCI) m/z 228[M+H+].

Workup

  1. stirringThe reaction mixture was stirred for 35 min
  2. customquenched with water
  3. extractionThe reaction mixture was extracted with ethyl acetate
  4. washthe organic layer was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. customevaporated in vacuo
  7. customPurification by column chromatography
  8. customyielded an oil
  9. customThe organic solvent was removed in vacuo
  10. temperaturethe residual aqueous solution was cooled on ice
  11. addition2 M hydrochloric acid was added until an acidic pH
  12. filtrationThe obtained precipitate was filtered off
  13. washwashed with ice-water
  14. customdried in vacuo

Sources & evidence

ORD record
ord-d612e598b7db435399b939fea012030a
Source dataset
uspto-grants-2012_03
Patent number
US08143408B2

Reaction notes

Loading…