Ethyl fluoroacetate → HCID 90404401, compound

HRID 924209Notes

Reaction equation

HRID 924209 reaction equation
[H-].[Na+].[F:3][CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].[F:10][C:11]([F:33])([F:32])[O:12][C:13]1[CH:18]=[CH:17][C:16]([N:19]2[CH:23]=[N:22][C:21]([C:24]3[CH:31]=[CH:30][C:27]([CH:28]=[O:29])=[CH:26][CH:25]=3)=[N:20]2)=[CH:15][CH:14]=1>>[F:3][CH:4]([CH:28]([OH:29])[C:27]1[CH:30]=[CH:31][C:24]([C:21]2[N:22]=[CH:23][N:19]([C:16]3[CH:17]=[CH:18][C:13]([O:12][C:11]([F:10])([F:33])[F:32])=[CH:14][CH:15]=3)[N:20]=2)=[CH:25][CH:26]=1)[C:5]([O:7][CH2:8][CH3:9])=[O:6]

Participants

4

Reactant 3

HCID 9988Ethyl fluoroacetateHCID 24758Sodium hydrideHCID 578244624-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzaldehyde

Product 1

HCID 90404401HCID 90404401, compound

Procedure

Sodium hydride (60% oil immersion, 0.48 g, 12 mmol) was added to a dry, oven-dried round bottomed flask and placed under nitrogen. Diethyl ether (9 mL) was added, followed by absolute ethanol (0.05 mL), and the reaction was cooled in an ice bath. Ethyl 2-fluoroacetate (0.87 mL, 9.0 mmol) was added dropwise. The reaction was stirred for 15 minutes in ice bath (gas evolution ceased). 4-(1-(4-(Trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzaldehyde (2.2 g, 6.5 mmol) was added in solid portions. The solution slowly turned color to a golden yellow. The ice bath was removed after 1 hour and warmed to room temperature, stirring for an additional 2 hours until the reaction was quenched with saturated aqueous ammonium chloride, diluted with diethyl ether, and stirred at room temperature for 3 days. The biphasic solution was diluted with brine and extracted with ethyl acetate (2×). The organic layers were dried organic over anhydrous sodium sulfate, filtered, and concentrated to give an orange liquid. The crude material was purified by reverse-phase flash column chromatography using 0-100% acetonitrile/water as eluent to afford the intermediate ethyl 2-fluoro-3-hydroxy-3-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)propanoate as a crude compound (0.11 g).

Workup

  1. customoven-dried round bottomed flask
  2. additionDiethyl ether (9 mL) was added
  3. temperaturethe reaction was cooled in an ice bath
  4. customThe ice bath was removed after 1 hour
  5. stirringstirring for an additional 2 hours until the reaction
  6. customwas quenched with saturated aqueous ammonium chloride
  7. additiondiluted with diethyl ether
  8. stirringstirred at room temperature for 3 days
  9. additionThe biphasic solution was diluted with brine
  10. extractionextracted with ethyl acetate (2×)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto give an orange liquid
  14. customThe crude material was purified by reverse-phase flash column chromatography

Sources & evidence

ORD record
ord-8ad3115b64954a688725cdba34c1f581
Source dataset
uspto-grants-2016_03
Patent number
US09278964B2

Reaction notes

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