Bromomethylcyclopropane → HCID 70570835, compound

HRID 1680238Notes

Reaction equation

HRID 1680238 reaction equation
C(=O)(O)[O-].[Na+].[ClH:6].[CH3:7][O:8][C:9]1[CH:10]=[CH:11][C:12]2[CH2:13][C@H:14]3[NH:25][CH2:24][CH2:23][C@@:20]4([C:21]=2[CH:22]=1)[C@@:15]3([O:28][CH3:29])[C@@H:16]([CH3:27])[CH2:17][C:18](=[O:26])[CH2:19]4.[CH:30]1([CH2:33]Br)[CH2:32][CH2:31]1>CN(C)C=O>[ClH:6].[CH:30]1([CH2:33][N:25]2[CH2:24][CH2:23][C@@:20]34[C:21]5[CH:22]=[C:9]([O:8][CH3:7])[CH:10]=[CH:11][C:12]=5[CH2:13][C@@H:14]2[C@:15]3([O:28][CH3:29])[C@@H:16]([CH3:27])[CH2:17][C:18](=[O:26])[CH2:19]4)[CH2:32][CH2:31]1

Participants

5

Reactant 3

HCID 81503BromomethylcyclopropaneHCID 516892Sodium BicarbonateHCID 70568077HCID 70568077, compound

Product 1

HCID 70570835HCID 70570835, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A slurry was made by the addition of sodium bicarbonate (1.24 g, 14.8 mol) to a solution of 3,14-dimethoxy-8β-methylmorphinan-6-one hydrochloride (37) (1.3 g, 3.7 mmol) and cyclopropylmethyl bromide (1 ml, 10.7 mmol) in 25 ml of dimethylformamide. This reaction mixture was heated at 100° C. under a nitrogen atmosphere, and after 16 hours the reaction mixture was cooled, sodium bicarbonate was removed by suction filtration and the filter cake washed thoroughly with dimethylformamide. After removal of the solvent by vacuum distallation (oil bath temperature 40°-45° C.), the residue was partitioned between ethyl acetate and water. The layers were separated and the aqueous phase was extracted with two additional portions of ethyl acetate. The organic fractions were combined, dried over Na2SO4 and concentrated under reduced pressure. Purification of the crude product by chromatography on Florisil (eluted with graded methanol/chloroform) yielded 1.0 g (75% theory) of the title compound as a golden oil. The hydrochloride salt of this compound was formed by taking up a sample of the oil in diethyl ether and adding ethereal hydrogen chloride to provide a colorless solid.

Workup

  1. temperatureafter 16 hours the reaction mixture was cooled
  2. customsodium bicarbonate was removed by suction filtration
  3. washthe filter cake washed thoroughly with dimethylformamide
  4. customAfter removal of the solvent by vacuum distallation (oil bath temperature 40°-45° C.)
  5. customthe residue was partitioned between ethyl acetate and water
  6. customThe layers were separated
  7. extractionthe aqueous phase was extracted with two additional portions of ethyl acetate
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated under reduced pressure
  10. customPurification of the crude product by chromatography on Florisil (eluted with graded methanol/chloroform)

Sources & evidence

ORD record
ord-8942373d0edd47afa95bd5de3a6ae04c
Source dataset
uspto-grants-1981_06
Patent number
US04272540

Reaction notes

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