2,2,2-Trifluoroethanol → HCID 86609536, compound

HRID 1865480Notes

Reaction equation

HRID 1865480 reaction equation
[H-].[Na+].[F:3][C:4]([F:8])([F:7])[CH2:5][OH:6].Cl[C:10]1[N:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[C:17]([CH3:25])[C:11]=1[C:12]([O:14][CH2:15][CH3:16])=[O:13]>C1COCC1>[CH3:25][C:17]1[C:11]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[C:10]([O:6][CH2:5][C:4]([F:8])([F:7])[F:3])[N:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=1

Participants

5

Reactant 3

HCID 64092,2,2-TrifluoroethanolHCID 24758Sodium hydrideHCID 18374283HCID 18374283, compound

Product 1

HCID 86609536HCID 86609536, compoundYield 55.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A suspension of sodium hydride (150 mg of 60% in mineral oil, 3.7 mmol) was formed in THF (10 mL) and cooled in an ice bath. 2,2,2-Trifluoroethanol (0.34 mL, 4.7 mmol) was added dropwise, then the mixture was stirred at 0° C. for 5 mins. A solution of ethyl 2-chloro4-methyl-6-(trifluoromethyl)nicotinate (500 mg, 1.9 mmol) in THF (10 mL) was added and the mixture heated at reflux for 18 hours then cooled to room temperature. The mixture was partitioned between ethyl acetate (100 mL) and water (100 mL). The organic phase was dried over magnesium sulphate, filtered and evaporated to give an oil. Purification by flash column chromatography on silica gel using 40% hexane: 60% DCM as eluent gave ethyl 4-methyl-2-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)nicotinate as a colourless oil (350 mg): 1H NMR (500 MHz, CDCl3): δ 7.24 (1H, s), 4.83-4.77 (2H, q, J 8.3), 4.43 (2H, q, J 7.1), 2.43 (3H, s), 1.38 (3H, t, J 7.1).

Workup

  1. temperaturecooled in an ice bath
  2. temperaturethe mixture heated
  3. temperatureat reflux for 18 hours
  4. temperaturethen cooled to room temperature
  5. customThe mixture was partitioned between ethyl acetate (100 mL) and water (100 mL)
  6. dry with materialThe organic phase was dried over magnesium sulphate
  7. filtrationfiltered
  8. customevaporated
  9. customto give an oil
  10. customPurification by flash column chromatography on silica gel using 40% hexane

Sources & evidence

ORD record
ord-bd643ec9186c48f68082acaa22bd7e78
Source dataset
uspto-grants-2009_12
Patent number
US07626056B2

Reaction notes

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