Tramadol → (+)-tramadol (R)-naproxen

HRID 1052945Notes

Reaction equation

HRID 1052945 reaction equation
[CH3:1][C@@H:2]([C:15]([OH:17])=[O:16])[C:3]1[CH:8]=[CH:7][C:6]2[CH:9]=[C:10]([O:13][CH3:14])[CH:11]=[CH:12][C:5]=2[CH:4]=1.[CH3:18][N:19]([CH2:21][C@@H:22]1[C@@:27]([OH:36])([C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([O:34][CH3:35])[CH:29]=2)[CH2:26][CH2:25][CH2:24][CH2:23]1)[CH3:20]>CO>[CH3:20][N:19]([CH2:21][C@@H:22]1[C@@:27]([OH:36])([C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([O:34][CH3:35])[CH:29]=2)[CH2:26][CH2:25][CH2:24][CH2:23]1)[CH3:18].[CH3:1][C@@H:2]([C:15]([OH:17])=[O:16])[C:3]1[CH:8]=[CH:7][C:6]2[CH:9]=[C:10]([O:13][CH3:14])[CH:11]=[CH:12][C:5]=2[CH:4]=1

Participants

4

Reactant 2

HCID 33741TramadolHCID 169118Naproxen, (-)-

Product 1

HCID 131736274(+)-tramadol (R)-naproxenYield 61.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A solution of (R)-naproxen (925 mg, 4.02 mmol) in 3 mL of methanol was added to a solution of (+)-tramadol (530 mg, 2.01 mmol) in 1 mL of methanol. The mixture was stirred for 10 minutes and about half of the solvent was evaporated. The resulting solution was left standing at room temperature and after 24 hours a solid had formed. The solid was filtered off, the filtrate was washed with 2 mL of methanol and dried under vacuum (10 mm Hg) for 4 hours to give the methanol solvate of the 1:2 co-crystal of (+)-tramadol-(R)-naproxen as crystalline white needles (610 mg, 42%).

Workup

  1. customwas evaporated
  2. waitThe resulting solution was left
  3. waitstanding at room temperature and after 24 hours
  4. customa solid had formed
  5. filtrationThe solid was filtered off
  6. washthe filtrate was washed with 2 mL of methanol
  7. customdried under vacuum (10 mm Hg) for 4 hours

Sources & evidence

ORD record
ord-a6032cd1162e45e580e7cd1ad548856c
Source dataset
uspto-grants-2016_07
Patent number
US09393220B2

Reaction notes

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