Tetrahydrofuran → 4-(2,3-Epoxypropyl)morpholine

HRID 2191485Notes

Reaction equation

HRID 2191485 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Cl[CH2:8][C@@H:9]1[O:11][CH2:10]1.CC(C)([O-])C.[K+].O1CCCC1>C(O)(C)(C)C>[O:11]1[CH2:10][CH:9]1[CH2:8][N:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 8083MorpholineHCID 2734062(-)-EpichlorohydrinHCID 23665647Potassium tert-butoxide

Product 1

HCID 977514-(2,3-Epoxypropyl)morpholineYield 88.8%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Procedure

Morpholine 53a (8.712 ml, 0.1 mol) was dissolved in tert-butanol (4.5 ml) under stirring at room temperature, and (R)-(−)-1-chloro-2,3-epoxypropane (8.05 ml, 0.1 mol) was added slowly to the solution at 0° C. in an ice-water bath. Upon completion of the addition, the ice-water bath was removed, and the reaction mixture was allowed to warm up to room temperature and stirred for 24 hours. After thin lay chromatography showed the disappearance of starting materials, the reaction mixture was added dropwise with a solution of potassium tert-butoxide in tetrahydrofuran (60 ml, 1.67 mol/L, 100 mmol) while maintaining the temperature below 10° C. in an ice-water bath, gradually turned from light yellow to white turbid solution and stirred for 30 minutes. After thin lay chromatography showed the disappearance of starting materials, the reaction mixture was concentrated under reduced pressure, added with water (50 ml), exacted with dichloromethane (100 ml×2). The combined organic extracts were washed with saturated brine (100 ml), dried over anhydrous magnesium sulfate, filtered to remove the drying agent and concentrated under reduced pressure to obtain the title compound 4-oxiranylmethyl-morpholine 53b (12.7 g, yield 88.8%) as a yellow oil.

Workup

  1. additionUpon completion of the addition
  2. customthe ice-water bath was removed
  3. temperatureto warm up to room temperature
  4. stirringstirred for 24 hours
  5. temperaturewhile maintaining the temperature below 10° C. in an ice-water bath
  6. stirringstirred for 30 minutes
  7. concentrationthe reaction mixture was concentrated under reduced pressure
  8. additionadded with water (50 ml)
  9. washThe combined organic extracts were washed with saturated brine (100 ml)
  10. dry with materialdried over anhydrous magnesium sulfate
  11. filtrationfiltered
  12. customto remove the drying agent
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-dfdfa56aa4564c5b99cb2fdd3e09702b
Source dataset
uspto-grants-2012_12
Patent number
US08329682B2

Reaction notes

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