Bromomethylcyclopropane → HCID 57147379, compound

HRID 1680221Notes

Reaction equation

HRID 1680221 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[CH2:7][C@H:8]3[NH:19][CH2:18][CH2:17][C@@:14]4([C:15]=2[CH:16]=1)[C@@:9]3([O:21][CH3:22])[CH2:10][CH2:11][C:12](=[O:20])[CH2:13]4.[CH:23]1([CH2:26]Br)[CH2:25][CH2:24]1.C([O-])(O)=O.[Na+]>CN(C=O)C>[CH:23]1([CH2:26][N:19]2[CH2:18][CH2:17][C@@:14]34[C:15]5[CH:16]=[C:3]([O:2][CH3:1])[CH:4]=[CH:5][C:6]=5[CH2:7][C@@H:8]2[C@:9]3([O:21][CH3:22])[CH2:10][CH2:11][C:12](=[O:20])[CH2:13]4)[CH2:25][CH2:24]1

Participants

5

Reactant 3

HCID 81503BromomethylcyclopropaneHCID 516892Sodium BicarbonateHCID 57240168HCID 57240168, compound

Product 1

HCID 57147379HCID 57147379, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 3,14-dimethoxymorphinan-6-one (6a) (4.491 g, 14.9 mmol), cyclopropylmethyl bromide (3.017 g, 22.35 mmol) and NaHCO3 (7.50 g, 89.4 mmol) in DMF (50 ml) was refluxed under nitrogen for 16 hours at 110° C. The mixture was filtered and the DMF removed by distillation under reduced pressure. The residue was taken up in methylene chloride (150 ml) and 150 ml of water. The two layers were separated and the aqueous layer re-extracted with methylene chloride (2×100 ml). The organic solutions were combined, washed with water (100 ml), dried over Na2SO4, filtered, and concentrated under reduced pressure. The resulting yellow solid was chromatographed on Florisil using graded methanol/chloroform as the eluant to give 17-cyclopropylmethyl-3,14-dimethoxymorphinan-6-one as a yellow oil which crystallized after drying the give 4.132 g (78% theory) of yellow solid. Recrystallization from ethanol gave 3.443 g (65%) of the title compound (8) (TR-5400) as colorless needles. A portion of 8 was converted to the hydrochloride salt (TR-5305) by treatment with ethereal hydrogen chloride to give a white solid, m.p. 215°-128° C.

Workup

  1. filtrationThe mixture was filtered
  2. customthe DMF removed by distillation under reduced pressure
  3. customThe two layers were separated
  4. extractionthe aqueous layer re-extracted with methylene chloride (2×100 ml)
  5. washwashed with water (100 ml)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting yellow solid was chromatographed on Florisil using graded methanol/chloroform as the eluant

Sources & evidence

ORD record
ord-0b8fc51363864e09a92925d9b049971d
Source dataset
uspto-grants-1981_06
Patent number
US04272540

Reaction notes

Loading…