Sodium Bicarbonate → HCID 57098303, compound

HRID 1680220Notes

Reaction equation

HRID 1680220 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:5]=[CH:6][C:7]2[CH2:8][C@H:9]3[NH:20][CH2:19][CH2:18][C@@:15]4([C:16]=2[CH:17]=1)[C@@:10]3([O:22][CH3:23])[CH2:11][CH2:12][C:13](=[O:21])[CH2:14]4.[CH:24]1([CH2:28]Br)[CH2:27][CH2:26][CH2:25]1.C([O-])(O)=O.[Na+]>CN(C)C=O>[CH:24]1([CH2:28][N:20]2[CH2:19][CH2:18][C@@:15]34[C:16]5[CH:17]=[C:4]([O:3][CH3:2])[CH:5]=[CH:6][C:7]=5[CH2:8][C@@H:9]2[C@:10]3([O:22][CH3:23])[CH2:11][CH2:12][C:13](=[O:21])[CH2:14]4)[CH2:27][CH2:26][CH2:25]1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 2734658(Bromomethyl)cyclobutaneHCID 70567751HCID 70567751, compound

Product 1

HCID 57098303HCID 57098303, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 3,14-dimethoxymorphinan-6-one hydrochloride (6b) (1.0 g, 2.96 mmol), cyclobutylmethyl bromide (0.662 g, 4.44 mmol) and NaHCO3 (1.492 g, 17.76 mmol) in 25 ml of dimethylformamide (DMF) was refluxed at an oil bath temperature of 110° under nitrogen for 16 hours. The mixture was filtered and the residue washed with DMF whereupon the filtrate was distilled under reduced pressure (oil bath temperature 30°-40° C.) and the residual material was taken up in methylene chloride (50 ml) and water (50 ml). The two layers were separated and the aqueous layer re-extracted with methylene chloride (2×50 ml). The organic layers were combined, washed with water (20 ml), dried over MgSO4, filtered and concentrated under reduced pressure. The resulting solid was chromatographed on Florisil, and eluted with graded methanol/chloroform mixtures to give 17-cyclobutylmethyl-3,14-dimethoxymorphinan-6-one as a yellow oil. This material was converted to its HCl salt (7) by treatment with ethereal hydrogen chloride to give 0.507 g of a light-colored solid (42% theory), m.p. 230° C. (decomposed).

Workup

  1. temperaturewas refluxed at an oil bath temperature of 110° under nitrogen for 16 hours
  2. filtrationThe mixture was filtered
  3. washthe residue washed with DMF whereupon the filtrate
  4. distillationwas distilled under reduced pressure (oil bath temperature 30°-40° C.)
  5. customThe two layers were separated
  6. extractionthe aqueous layer re-extracted with methylene chloride (2×50 ml)
  7. washwashed with water (20 ml)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe resulting solid was chromatographed on Florisil
  12. washeluted with graded methanol/chloroform mixtures

Sources & evidence

ORD record
ord-c2518eda6bf146a3bfae76ed87e1e589
Source dataset
uspto-grants-1981_06
Patent number
US04272540

Reaction notes

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