Potassium Carbonate → 3-Methoxynaltrexone

HRID 1051165Notes

Reaction equation

HRID 1051165 reaction equation
[OH:1][C@:2]12[C@H:11]3[CH2:12][C:13]4[C:18]5[C@@:7]1([CH2:8][CH2:9][NH:10]3)[C@@H:6]([O:19][C:17]=5[C:16]([O:20][CH3:21])=[CH:15][CH:14]=4)[C:5](=[O:22])[CH2:4][CH2:3]2.C([O-])([O-])=O.[K+].[K+].[CH:29]1([CH2:32]Br)[CH2:31][CH2:30]1>CC#N>[CH:29]1([CH2:32][N:10]2[CH2:9][CH2:8][C@@:7]34[C:18]5[C:13]6[CH2:12][C@@H:11]2[C@:2]3([OH:1])[CH2:3][CH2:4][C:5](=[O:22])[C@@H:6]4[O:19][C:17]=5[C:16]([O:20][CH3:21])=[CH:15][CH:14]=6)[CH2:31][CH2:30]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 81503BromomethylcyclopropaneHCID 5489120Noroxycodone

Product 1

HCID 54876953-Methoxynaltrexone

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a suspension of Compound 3 (9.5 g, 31.5 mmol) in 80 mL of CH3CN was added K2CO3 (10.9 g, 79.0 mmol) portionwise followed by cyclopropylmethyl bromide (3.97 mL, 41.0 mmol) dropwise via syringe. The suspension was heated at reflux for 18 h. LC-MS showed a single peak corresponding to the desired product (Tr=0.830 min, M+H=356). The mixture was cooled to ambient temperature and the solid was filtered off and washed with CH3CN. The filtrate was concentrated and the golden yellow residue was diluted with CH2Cl2 and H2O. The layers were separated and the aqueous was further extracted with CH2Cl2. The combined organics were washed with brine, dried over MgSO4, filtered, and concentrated to provide 9.76 g (87%) of Compound 4 as a white foam that turned to a light yellow oily foam overnight. LC/MS, m/z=356.2 [M+H]+ (Calc: 356.43).

Workup

  1. temperatureThe suspension was heated
  2. temperatureat reflux for 18 h

Sources & evidence

ORD record
ord-3ed5e977b17045a7bb16c802cfe2e1a9
Source dataset
uspto-grants-2016_07
Patent number
US09388162B2

Reaction notes

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