Sodium Bicarbonate → HCID 70590735, compound

HRID 224355Notes

Reaction equation

HRID 224355 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:5]=[CH:6][C:7]2[CH2:8][C@H:9]3[NH:21][CH2:20][CH2:19][C@:15]45[C:16]=2[C:17]=1[O:18][C@H:14]4[C:13](=[O:22])[CH2:12][C@@H:11]([CH3:23])[C@@:10]35[O:24][CH3:25].[CH:26]1([CH2:30]Br)[CH2:29][CH2:28][CH2:27]1.C(=O)(O)[O-].[Na+]>CN(C)C=O>[CH:26]1([CH2:30][N:21]2[CH2:20][CH2:19][C@:15]34[C:16]5[C:17]6[O:18][C@H:14]3[C:13](=[O:22])[CH2:12][C@@H:11]([CH3:23])[C@@:10]4([O:24][CH3:25])[C@H:9]2[CH2:8][C:7]=5[CH:6]=[CH:5][C:4]=6[O:3][CH3:2])[CH2:29][CH2:28][CH2:27]1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 2734658(Bromomethyl)cyclobutaneHCID 70590744HCID 70590744, compound

Product 1

HCID 70590735HCID 70590735, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 3,14-dimethoxy-4,5α-epoxy-8α-methylmorphinan-6-one hydrochloride (4) (3.4 g, 9.29 mmol), cyclobutylmethyl bromide (3.4 g, 22.8 mmol), sodium bicarbonate (5.0 g, 59.5 mmol) and 100 milliliters of dimethylformamide was heated at 105° to 100° C. while being stirred and maintained under a nitrogen atmosphere. The reaction mixture was heated for 18 hours, after which the inorganic material was removed by filtration and the filter cake was washed twice with dimethylformamide (100 ml). The filtrate and washings were combined and distilled under high vacuum (bath temperatures 35° C.) and the material which remained was taken up with ethyl acetate (300 ml)/H2O (80 ml) and made basic by the addition of saturated sodium bicarbonate solution. After separating the organic layer, the aqueous phase was re-extracted with ethyl acetate (2×150 ml). The combined ethyl acetate extracts were dried over MgSO4, filtered and concentrated under reduced pressure to give 3.1 g (84% theory) of the crude desired product. This material was purified by chromatography on silica gel using benzene followed by 50:50 benzene/chloroform, chloroform and graded (2% to 50%) methanol/chloroform mixtures. Those fractions containing pure product were combined and evaporated to give 1.39 g (38% theory) of the desired compound as a foamy solid. A portion of the product was converted to the hydrochloride salt by treatment with ethereal hydrogen chloride.

Workup

  1. temperaturewas heated at 105° to 100° C.
  2. temperaturemaintained under a nitrogen atmosphere
  3. temperatureThe reaction mixture was heated for 18 hours
  4. customafter which the inorganic material was removed by filtration
  5. washthe filter cake was washed twice with dimethylformamide (100 ml)
  6. distillationdistilled under high vacuum (bath temperatures 35° C.)
  7. additionmade basic by the addition of saturated sodium bicarbonate solution
  8. customAfter separating the organic layer
  9. extractionthe aqueous phase was re-extracted with ethyl acetate (2×150 ml)
  10. dry with materialThe combined ethyl acetate extracts were dried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customto give 3.1 g (84% theory) of the crude desired product
  14. customThis material was purified by chromatography on silica gel
  15. additionThose fractions containing pure product
  16. customevaporated

Sources & evidence

ORD record
ord-495472b6e1154fd58c725bc250653cab
Source dataset
uspto-grants-1980_11
Patent number
US04232028

Reaction notes

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