Reaction #1140126

Reaction equation

(R)-naproxen

(+)-tramadol

→

(+)-tramadol (R)-naproxen

Solvents

methanol

methanol

Conditions

Workup

1. 1
   Otherthe solvent was evaporated under vacuum
2. 2
   workup.STIRRINGstirred for 7 days at room temperature
3. 3
   FiltrationThe resulting suspension was filtered off
4. 4
   WashThe filtrate was washed with 5 mL of diisopropyl ether
5. 5
   Otherdried under vacuum at 40° C. (10 mm Hg) for 16 hours

Procedure

A solution of (R)-naproxen (751 mg, 3.26 mmol) in 4 mL of methanol was added to a solution of (+)-tramadol (430 mg, 1.63 mmol) in 1 mL of methanol. The mixture was stirred for 30 minutes and the solvent was evaporated under vacuum rendering an oil, which solidified by cooling to −197° C. The resulting solid was suspended in 10 mL of diisopropyl ether and stirred for 7 days at room temperature. The resulting suspension was filtered off. The filtrate was washed with 5 mL of diisopropyl ether and dried under vacuum at 40° C. (10 mm Hg) for 16 hours to give a co-crystal of (+)-tramadol-(R)-naproxen in a 1:2 ratio as a crystalline white solid (620 mg, 53%).

Source