Chloromethyl ethyl ether → HCID 53744314, compound

HRID 1738915Notes

Reaction equation

HRID 1738915 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5](=[O:19])[NH:6][CH:7]([CH2:11][C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=1)[CH2:8][CH:9]=[CH2:10].[CH2:20]([O:22][CH2:23]Cl)[CH3:21]>O1CCCC1>[CH3:3][O:4][C:5](=[O:19])[N:6]([CH:7]([CH2:11][C:12]1[CH:13]=[CH:14][C:15]([Cl:18])=[CH:16][CH:17]=1)[CH2:8][CH:9]=[CH2:10])[CH2:23][O:22][CH2:20][CH3:21]

Participants

5

Reactant 3

HCID 18523Chloromethyl ethyl etherHCID 24758Sodium hydrideHCID 67597686HCID 67597686, compound

Product 1

HCID 53744314HCID 53744314, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A suspension of 10.0 g of sodium hydride (80% in mineral oil, 333 mmol) in dry tetrahydrofuran [THF] is heated at reflux under argon. A solution of 60.5 g (238 mmol) of [1-(4-chloro-benzyl)-but-3-enyl]-carbamic acid methyl ester [McCarty F J, Rosenstock P D, Paolini J P, Micucci D D, Ashton L, Bennetts W W, J. Med. Chem, 1968, 11(3),534] in 50 ml of dry THF is added dropwise thereto in the course of 1 hour. The mixture is then boiled under reflux for 2 hours until the evolution of gas subsides. The mixture is cooled to 0° C. and chloromethyl ethyl ether is added dropwise in such a manner that the reaction temperature does not exceed 5° C. The mixture is then heated slowly to 25° C. and stirred for 12 hours to complete the reaction. Excess sodium hydride is destroyed carefully with 1 ml of water before more water is added. The phases are separated and the aqueous phase is extracted again with tert-butyl methyl ether. The combined organic phases are washed with brine, dried over sodium sulfate, and concentrated by evaporation. The crude product is distilled at 0.1 mbar and has a boiling range of 120-125° C. TLC: ethyl acetate/hexane (1:6) Rf =0.34, FD-MS: M+ =311 (313).

Workup

  1. temperatureis heated
  2. temperatureat reflux under argon
  3. customin the course of 1 hour
  4. temperatureunder reflux for 2 hours until the evolution of gas subsides
  5. customdoes not exceed 5° C
  6. temperatureThe mixture is then heated slowly to 25° C.
  7. customthe reaction
  8. customExcess sodium hydride is destroyed carefully with 1 ml of water before more water
  9. additionis added
  10. customThe phases are separated
  11. extractionthe aqueous phase is extracted again with tert-butyl methyl ether
  12. washThe combined organic phases are washed with brine
  13. dry with materialdried over sodium sulfate
  14. concentrationconcentrated by evaporation
  15. distillationThe crude product is distilled at 0.1 mbar

Sources & evidence

ORD record
ord-121d7efc9bfe451f8561b65565c28eec
Source dataset
uspto-grants-1999_10
Patent number
US05965562

Reaction notes

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