Water → Naloxone 3-methyl ether

HRID 1051164Notes

Reaction equation

HRID 1051164 reaction equation
[CH2:1]=[CH:2][CH2:3][N:4]1[C@@H:21]2[CH2:22][C:9]3[CH:10]=[CH:11][C:12]([OH:24])=[C:13]4[O:14][C@H:15]5[C:16]([CH2:18][CH2:19][C@:20]2([OH:23])[C@:7]5([C:8]=34)[CH2:6][CH2:5]1)=[O:17].[C:25]([O-])([O-])=O.[K+].[K+].CI.O>CN(C=O)C.C(Cl)Cl>[CH2:3]([N:4]1[CH2:5][CH2:6][C@@:7]23[C:8]4[C:9]5[CH2:22][C@@H:21]1[C@:20]2([OH:23])[CH2:19][CH2:18][C:16](=[O:17])[C@@H:15]3[O:14][C:13]=4[C:12]([O:24][CH3:25])=[CH:11][CH:10]=5)[CH:2]=[CH2:1]

Participants

7

Reactant 4

HCID 962Water2×HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 5284596Naloxone

Product 1

HCID 11056967Naloxone 3-methyl etherYield 66%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a solution of naloxone (50 g, 125 mmol) in 50 mL of DMF was added K2CO3 (51.8 g, 375 mmol). The resulting suspension was stirred at ambient temperature for 30 min whereupon methyl iodide (7.82 mL, 125 mmol) in 7 mL of DMF was added dropwise via an addition funnel. The suspension was maintained overnight at ambient temperature. The reaction mixture was added to 1 L of H2O and a white precipitate formed. The mixture was stirred for 1 h then filtered to give a white solid. The solid was dissolved in CH2Cl2 (700 mL) and washed with 1 N NaOH (400 mL). The layers were separated and the organic layer was concentrated to give a wet solid. Water was added and the solid was subsequently filtered and dried overnight in a vacuum oven to afford 28.1 g (66%) of Compound 2 as a white solid. LC/MS, m/z=342.2 [M+H]+ (Calc: 342.40).

Workup

  1. additionwas added dropwise via an addition funnel
  2. customa white precipitate formed
  3. filtrationthen filtered
  4. customto give a white solid
  5. washwashed with 1 N NaOH (400 mL)
  6. customThe layers were separated
  7. concentrationthe organic layer was concentrated
  8. customto give a wet solid
  9. filtrationthe solid was subsequently filtered
  10. customdried overnight in a vacuum oven

Sources & evidence

ORD record
ord-fda796a091914e24aa6f48bc3f804bcc
Source dataset
uspto-grants-2016_07
Patent number
US09388162B2

Reaction notes

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