Ethylene Glycol → HCID 10536881, compound

HRID 1479194Notes

Reaction equation

HRID 1479194 reaction equation
[H-].[Na+].[CH2:3]([OH:6])[CH2:4][OH:5].[H][H].Br[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=1.[Cl-].[NH4+]>C1COCC1.CCCCCC>[F:18][C:17]([F:19])([F:20])[C:14]1[CH:15]=[CH:16][C:11]([CH2:10][O:5][CH2:4][CH2:3][OH:6])=[CH:12][CH:13]=1

Participants

8

Reactant 5

HCID 174Ethylene GlycolHCID 24758Sodium hydride2×HCID 25517Ammonium ChlorideHCID 1230621-(Bromomethyl)-4-(trifluoromethyl)benzeneHCID 178418361HCID 178418361, compound

Product 1

HCID 10536881HCID 10536881, compoundYield 84%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent2×

Procedure

Under argon atmosphere, at r.t., sodium hydride (60% dispersion in mineral oil, 1.92 g, 48 mmol) was stirred with n-hexane (ca. 10 ml). The hexane/mineral oil solution was drawn off and discarded and the left sodium hydride was treated with 20 ml of dry THF. Ethylene glycol (17.8 ml, 320 mmol) was then slowly dropped at r.t. (caution: hydrogen evolution) and the mixture stirred at r.t. for 1.5 hours. After heating up to reflux (80° C. oil bath) a solution of 1-bromomethyl-4-trifluoromethyl-benzene (7.6 g, 32 mmol) in 20 ml of dry THF was added and the reaction mixture stirred at reflux for 2.5 hours. After cooling to r.t., 100 ml of ammonium chloride saturated solution was added. The organic layer was separated, washed with 50 ml of water, dried over sodium sulfate and evaporated to dryness. The crude residue was purified by flash chromatography (Biotage SP1 Flash Purification system) on a silica gel cartridge (Varian SF40-120 g) using n-hexane as eluant A and EtOAc as eluant B. Elution with a gradient from A/B 75:25 to 70:30 over 2 CV then from 70:30 to 0:100 over 2 CV then 100% of B afforded 5.9 g (yield: 84%) of the title compound as a yellow oil (yield: 93%).

Workup

  1. temperatureAfter heating up
  2. additionwas added
  3. stirringthe reaction mixture stirred
  4. temperatureat reflux for 2.5 hours
  5. temperatureAfter cooling to r.t.
  6. customThe organic layer was separated
  7. washwashed with 50 ml of water
  8. dry with materialdried over sodium sulfate
  9. customevaporated to dryness
  10. customThe crude residue was purified by flash chromatography (Biotage SP1 Flash Purification system) on a silica gel cartridge (Varian SF40-120 g)
  11. washElution with a gradient from A/B 75:25 to 70:30 over 2 CV

Sources & evidence

ORD record
ord-43f1e50129fd4246909fa3cb6d429e0a
Source dataset
uspto-grants-2016_08
Patent number
US09408850B2

Reaction notes

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