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

HRID 623501Notes

Reaction equation

HRID 623501 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 71.8%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent2×

Procedure

To a stirred suspension of sodium hydride (4.9 g, 120 mmol, 60% in oil) in N,N-dimethylacetamide (100 mL) is added dropwise 2,2,3,3,3-pentafluoropropan-1-ol (8.1 mL, 82 mmol) at 0° C. After stirring for 10 minutes, a solution of methyl 6-chloronicotinate (7.0 g, 41 mmol) in N,N-dimethylacetamide (120 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 to give 8.4 g of the title compound as a crude product (include 2,2,3,3,3-pentafluoropropyl 6-(2,2,3,3,3-pentafluoropropoxy)nicotinate as a byproduct). The residue is used for the next reaction (Step-2) without further purification.

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

Sources & evidence

ORD record
ord-b9f5a949e7f5462eae306efa5f86caf3
Source dataset
uspto-grants-2016_04
Patent number
US09302991B2

Reaction notes

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