2,2,3,3-Tetrafluoro-1-propanol → Ethyl 6-(2,2,3,3-tetrafluoropropoxy)nicotinate

HRID 381438Notes

Reaction equation

HRID 381438 reaction equation
[H-].[Na+].[F:3][C:4]([F:10])([CH:7]([F:9])[F:8])[CH2:5][OH:6].[H][H].Cl[C:14]1[CH:24]=[CH:23][C:17]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:16][N:15]=1>CCCCCC.CN(C)C=O>[F:3][C:4]([F:10])([CH:7]([F:9])[F:8])[CH2:5][O:6][C:14]1[CH:24]=[CH:23][C:17]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:16][N:15]=1

Participants

7

Reactant 4

HCID 64412,2,3,3-Tetrafluoro-1-propanolHCID 24758Sodium hydrideHCID 2799611Ethyl 6-chloronicotinateHCID 178418361HCID 178418361, compound

Product 1

HCID 18363323Ethyl 6-(2,2,3,3-tetrafluoropropoxy)nicotinateYield 86%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8058HexaneSolvent

Procedure

After 840 mg (19.3 mmol) of 55% sodium hydride were washed with hexane, it was suspended in 40 ml of dimethylformamide, and 3.00 g (22.7 mmol) of 2,2,3,3-tetrafluoropropanol were gradually added to the suspension at 0° C. under a nitrogen atmosphere. When generation of hydrogen gas stopped a solution in which 3.40 g (18.3 mmol) of ethyl 6-chloronicotinate was dissolved in 15 ml of dimethylformamide was added dropwise to the resulting mixture at the same temperature for about 30 minutes. After the dropwise addition, the mixture was stirred for 30 minutes and the reaction mixture was poured into ice-water, followed by extraction with benzene. After the extract was dried, the solvent was distilled off and the thus obtained oil was purified over column chromatography [eluted with a mixed solvent of benzene-hexane (1:1)] using silica gel to obtain 4.42 g (yield: 86%) of the title compound as an oil.

Workup

  1. additionwas added dropwise to the resulting mixture at the same temperature for about 30 minutes
  2. additionAfter the dropwise addition
  3. extractionfollowed by extraction with benzene
  4. customAfter the extract was dried
  5. distillationthe solvent was distilled off
  6. customthe thus obtained oil was purified over column chromatography [
  7. washeluted with a mixed solvent of benzene-hexane (1:1)]

Sources & evidence

ORD record
ord-7b842af790c44a48bc585def63b6d257
Source dataset
uspto-grants-2001_10
Patent number
US06306880B1

Reaction notes

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