Diethyl Ether → 8-Hydroxy-8-methyl-5-(propan-2-yl)non-6-en-2-one

HRID 648385Notes

Reaction equation

HRID 648385 reaction equation
[Li].[CH3:2]Br.[CH:4]([CH:7]([CH:12]=[CH:13][C:14](=[O:16])[CH3:15])[CH2:8][CH2:9]C#N)([CH3:6])[CH3:5].[Cl-].[NH4+].C([O:21][CH2:22][CH3:23])C>C1(C)C=CC=CC=1>[OH:16][C:14]([CH3:15])([CH3:2])[CH:13]=[CH:12][CH:7]([CH:4]([CH3:5])[CH3:6])[CH2:8][CH2:9][C:22](=[O:21])[CH3:23]

Participants

7

Reactant 5

HCID 3283Diethyl EtherHCID 6323Methyl Bromide2×HCID 25517Ammonium ChlorideHCID 3028194Lithium3×HCID 542053137-Oxo-4-(propan-2-yl)oct-5-enenitrile

Product 1

HCID 541591768-Hydroxy-8-methyl-5-(propan-2-yl)non-6-en-2-one

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

Into a 12-liter reaction vessel equipped with stirrer, thermometer, condenser, gas addition tube (straight, not a dispersion tube), heating mantle and nitrogen blanket apparatus, is placed 4.5 liters of diethylether anhydrous and 120 grams (17.4 moles) of 4-16 mesh lithium shot. The contents of the flask are stirred and refluxed for one hour in order to activate the lithium. The heating mantle is removed and the contents of the flask are allowed to cool to room temperature. 828 grams (8.7 moles) of methyl bromide gas is then added to the reaction mass over a six hour period at a rate such that little gas escapes from the top of the condenser. The reaction is exothermic and will cause the solvent to reflux. When the addition of the methyl bromide is complete and the lithium has dissolved, one liter of toluene is added to the reaction mass. The resulting mixture is cooled to 0°-5° C. and the gas addition tube is replaced by an addition funnel. A toluene solution containing 470 grams of 4-isopropyl-7-oxo- 5-octenenitrile prepared according to Example IV is added dropwise to the reaction mass over a one hour period while maintaining the reaction mass at 0°-5° C. When addition is complete, the reaction mass is allowed to warm to room temperature. A GLC sample at this point shows no starting material and no nitrile present. When the reaction is complete, 800 ml of saturated ammonium chloride solution is added to the reaction mass with stirring. The resulting mixture is stirred for one hour and the organic layer is separated from the aqueous layer. The diethylether solvent is stripped from the reaction mass and the reaction mass is distilled through an 8" stone-packed column yielding the following fractions:

Workup

  1. customInto a 12-liter reaction vessel
  2. customequipped with stirrer
  3. additionthermometer, condenser, gas addition tube (straight, not a dispersion tube),
  4. temperatureheating mantle and nitrogen blanket apparatus
  5. temperaturerefluxed for one hour in order
  6. customThe heating mantle is removed
  7. temperatureto reflux
  8. temperatureThe resulting mixture is cooled to 0°-5° C.
  9. additionthe gas addition tube
  10. customis replaced by an addition funnel
  11. customprepared
  12. additionis added dropwise to the reaction mass over a one hour period
  13. temperaturewhile maintaining the reaction mass at 0°-5° C
  14. additionWhen addition
  15. temperatureto warm to room temperature
  16. stirringwith stirring
  17. stirringThe resulting mixture is stirred for one hour
  18. customthe organic layer is separated from the aqueous layer
  19. distillationthe reaction mass is distilled through an 8" stone-packed column
  20. customyielding the following fractions

Sources & evidence

ORD record
ord-c8b45042cee9477fbce4f59130e99283
Source dataset
uspto-grants-1983_10
Patent number
US04412083

Reaction notes

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