HCID 57085542, compound → HCID 70569826, compound

HRID 1680235Notes

Reaction equation

HRID 1680235 reaction equation
[CH3:1][Li].[CH3:3][O:4][C:5]1[CH:6]=[CH:7][C:8]2[CH2:9][C@H:10]3[N:21]([CH3:22])[CH2:20][CH2:19][C@@:16]4([C:17]=2[CH:18]=1)[C@@:11]3([O:24][CH3:25])[CH:12]=[CH:13][C:14](=[O:23])[CH2:15]4>C(OCC)C.C(Cl)Cl.[Cu](I)I>[CH3:3][O:4][C:5]1[CH:6]=[CH:7][C:8]2[CH2:9][C@H:10]3[N:21]([CH3:22])[CH2:20][CH2:19][C@@:16]4([C:17]=2[CH:18]=1)[C@@:11]3([O:24][CH3:25])[C@@H:12]([CH3:1])[CH2:13][C:14](=[O:23])[CH2:15]4

Participants

6

Reactant 2

HCID 57085542HCID 57085542, compoundHCID 178418348HCID 178418348, compound

Product 1

HCID 70569826HCID 70569826, compound

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 3283Diethyl EtherSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
-20 °C

Procedure

A slurry of copper iodide (8.63 g, 0.045 mol) in 250 ml of anhydrous diethyl ether was cooled at -20° to -25° C. in a dry ice/carbon tetrachloride bath while being held under a nitrogen atmosphere. Methyl lithium (49.3 ml of a 1.84 M solution in ether, 0.091 mol) was cannulated into a calibrated dropping funnel and quickly added to the slurry. This complex was cooled an additional 10 minutes at -25° C. before a solution of 7,8-didehydro-3,14-dimethoxy-17-methylmorphinan-6-one (3) (9.47 g, 0.032 mol) in 60 ml of dry methylene chloride was added dropwise and washed in with an additional 30 ml of dry diethyl ether. After stirring at -20° C. for 21/2 hours, the reaction mixture was quenched with 60 ml of 20% ammonium hydroxide and made basic by the addition of 50% sodium hydroxide. The resultant copper salts were removed by suction filtration and the filter cake was washed several times with diethyl ether and water. The layers were separated and the aqueous phase extracted with two additional portions of ether. The ethereal extracts were combined, washed with saturated sodium chloride solution, dried over Na2SO4 and concentrated under reduced pressure. Purification by chromatography on Flosisil (eluted with graded methanol/chloroform) yielded 4.6 g (46% theory) of the title compound.

Workup

  1. additionquickly added to the slurry
  2. additionwas added dropwise
  3. washwashed in with an additional 30 ml of dry diethyl ether
  4. customthe reaction mixture was quenched with 60 ml of 20% ammonium hydroxide
  5. additionmade basic by the addition of 50% sodium hydroxide
  6. customThe resultant copper salts were removed by suction filtration
  7. washthe filter cake was washed several times with diethyl ether and water
  8. customThe layers were separated
  9. extractionthe aqueous phase extracted with two additional portions of ether
  10. washwashed with saturated sodium chloride solution
  11. dry with materialdried over Na2SO4
  12. concentrationconcentrated under reduced pressure
  13. customPurification by chromatography
  14. washon Flosisil (eluted with graded methanol/chloroform)

Sources & evidence

ORD record
ord-18046428fca54fbd91fb008e143a4ae7
Source dataset
uspto-grants-1981_06
Patent number
US04272540

Reaction notes

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