2,2,3,3,3-Pentafluoropropanol → HCID 87426740, compound

HRID 623497Notes

Reaction equation

HRID 623497 reaction equation
[H-].[Na+].[F:3][C:4]([F:11])([C:7]([F:10])([F:9])[F:8])[CH2:5][OH:6].Cl[C:13]1[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][N:14]=1.[OH-].[Na+]>CN(C)C(=O)C>[F:3][C:4]([F:11])([C:7]([F:10])([F:9])[F:8])[CH2:5][O:6][C:13]1[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][N:14]=1

Participants

6

Reactant 4

HCID 98722,2,3,3,3-PentafluoropropanolHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 254249Methyl 6-chloropyridine-3-carboxylate

Product 1

HCID 87426740HCID 87426740, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent2×

Procedure

To a stirred suspension of sodium hydride (3.9 g, 96 mmol, 60% in oil) in N,N-dimethylacetamide (160 mL) is added dropwise 2,2,3,3,3-pentafluoropropan-1-ol (6.4 mL, 64 mmol) at 0° C. After stirring for 10 minutes, a solution of methyl 6-chloronicotinate (5.5 g, 32 mmol) in N,N-dimethylacetamide (10 mL) is added dropwise at 0° C., and the mixture is stirred for 30 minutes at room temperature. Then, the mixture is stirred at 90° C. for 2 hours. After cooled to room temperature, 2M aqueous sodium hydroxide is added (pH is around 6). The mixture is extracted with n-hexane/ethyl acetate (1:2, 200 mL). The organic layer is washed with water, brine, and dried over sodium sulfate. The organic solvent is concentrated under reduced pressure, and the residue is purified by column chromatography on amine gel eluting with n-hexane/ethyl acetate (30:1) to give 3.1 g (34% yield) of the title compound as brown oil. MS (ESI) m/z: 286 (M+H)+.

Workup

  1. stirringthe mixture is stirred for 30 minutes at room temperature
  2. stirringThen, the mixture is stirred at 90° C. for 2 hours
  3. extractionThe mixture is extracted with n-hexane/ethyl acetate (1:2, 200 mL)
  4. washThe organic layer is washed with water, brine
  5. dry with materialdried over sodium sulfate
  6. concentrationThe organic solvent is concentrated under reduced pressure
  7. customthe residue is purified by column chromatography on amine gel
  8. washeluting with n-hexane/ethyl acetate (30:1)

Sources & evidence

ORD record
ord-836b0a1b883f464d9d37c01bb23cbd6f
Source dataset
uspto-grants-2016_04
Patent number
US09302991B2

Reaction notes

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