Hydrochloric Acid → HCID 70568426, compound

HRID 1680231Notes

Reaction equation

HRID 1680231 reaction equation
[ClH:1].[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:23][CH3:24])[C@H:11]([CH3:22])[CH2:12][C:13](=[O:21])[CH2:14]4.C(=O)(O)[O-].[Na+].[CH2:30](Br)[CH:31]1[O:35][CH2:34][CH2:33][CH2:32]1.Cl>CN(C)C=O>[ClH:1].[CH2:30]([N:20]1[CH2:19][CH2:18][C@@:15]23[C:16]4[CH:17]=[C:4]([O:3][CH3:2])[CH:5]=[CH:6][C:7]=4[CH2:8][C@@H:9]1[C@:10]2([O:23][CH3:24])[C@H:11]([CH3:22])[CH2:12][C:13](=[O:21])[CH2:14]3)[CH:31]1[O:35][CH2:34][CH2:33][CH2:32]1

Participants

6

Reactant 4

HCID 313Hydrochloric Acid2×HCID 14501Furan, 2-(bromomethyl)tetrahydro-HCID 516892Sodium BicarbonateHCID 70567811HCID 70567811, compound

Product 1

HCID 70568426HCID 70568426, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 3,14-dimethoxy-8α-methylmorphinan-6-one hydrochloride (26) (0.24 g, 0.68 mmol), sodium bicarbonate (0.6 g, 7.14 mmol), (+) tetrahydrofurfuryl bromide (0.4 g, 2.42 mmol) and dimethylformamide (15 ml) was heated at 110° C. for 16 hours with stirring under a nitrogen atmosphere. The mixture was filtered hot and the residue washed with 10 milliliters of dimethylformamide. Most of the DMF was removed by distillation under high vacuum (bath temperature 35° C.) and the resulting brownish material was treated with CHCl3 (50 ml) and water (25 ml). After separation of the two layers, the aqueous layer was saturated with sodium chloride and re-extracted with ethyl acetate (3×25 ml). The organic extracts were combined, dried (MgSO4) and filtered. The filtrate was concentrated to an oily solid which was chromatographed over silica gel to give a mixture of R and S isomers of the product; yield 0.181 g (66.5% theory). A portion of the free base was converted to the HCl salt by treatment with ethereal HCl to form the title compound as a tan solid.

Workup

  1. filtrationThe mixture was filtered hot
  2. washthe residue washed with 10 milliliters of dimethylformamide
  3. customMost of the DMF was removed by distillation under high vacuum (bath temperature 35° C.)
  4. additionthe resulting brownish material was treated with CHCl3 (50 ml) and water (25 ml)
  5. customAfter separation of the two layers
  6. extractionre-extracted with ethyl acetate (3×25 ml)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated to an oily solid which
  10. customwas chromatographed over silica gel
  11. customto give
  12. additiona mixture of R and S isomers of the product

Sources & evidence

ORD record
ord-fccac838971f4e63990a44dc6eb87766
Source dataset
uspto-grants-1981_06
Patent number
US04272540

Reaction notes

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