Sodium hydride → (S)-3-(2-(4-(5-bromo-2-chlorobenzyl)phenoxy)ethoxy)tetrahydrofuran

HRID 2403757Notes

Reaction equation

HRID 2403757 reaction equation
[O:1]1[CH2:5][CH2:4][C@@H:3]([OH:6])[CH2:2]1.[H-].[Na+].CC1C=CC(S(O[CH2:20][CH2:21][O:22][C:23]2[CH:28]=[CH:27][C:26]([CH2:29][C:30]3[CH:35]=[C:34]([Br:36])[CH:33]=[CH:32][C:31]=3[Cl:37])=[CH:25][CH:24]=2)(=O)=O)=CC=1>O1CCCC1>[Br:36][C:34]1[CH:33]=[CH:32][C:31]([Cl:37])=[C:30]([CH:35]=1)[CH2:29][C:26]1[CH:25]=[CH:24][C:23]([O:22][CH2:21][CH2:20][O:6][C@H:3]2[CH2:4][CH2:5][O:1][CH2:2]2)=[CH:28][CH:27]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 641512(-)-3-HydroxytetrahydrofuranHCID 595577472-(4-(5-Bromo-2-chlorobenzyl)phenoxy)ethyl 4-methylbenzenesulfonate

Product 1

HCID 66704611(S)-3-(2-(4-(5-bromo-2-chlorobenzyl)phenoxy)ethoxy)tetrahydrofuranYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of (R)-tetrahydrofuran-3-ol (320 mg, 3.63 mmol) in dry tetrahydrofuran (10 mL) was added sodium hydride (145 mg, 3.63 mmol, 60%) slowly under 0° C. The reaction was stirred at this temperature for 30 min and then 2-(4-(5-bromo-2-chlorobenzyl)phenoxy)ethyl 4-methylbenzenesulfonate (intermediate AB) (300 mg, 0.61 mmol was added. The reaction was warmed to room temperature and then heated to reflux overnight. The reaction was quenched with saturated ammonium chloride and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated to a yellow oil. The crude oil was purified by flash chromatography to get 200 mg of colorless oil (80% yield).

Workup

  1. temperatureheated
  2. temperatureto reflux overnight
  3. customThe reaction was quenched with saturated ammonium chloride
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated to a yellow oil
  8. customThe crude oil was purified by flash chromatography

Sources & evidence

ORD record
ord-02f4453b72b4449b88ca8c518b4c5274
Source dataset
uspto-grants-2014_08
Patent number
US08802637B2

Reaction notes

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