Tramadol → (+)-tramadol (R)-naproxen

HRID 1052944

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

Conditions

Temperature: -197 °C

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%).

Workup

customthe solvent was evaporated under vacuum
stirringstirred for 7 days at room temperature
filtrationThe resulting suspension was filtered off
washThe filtrate was washed with 5 mL of diisopropyl ether
customdried under vacuum at 40° C. (10 mm Hg) for 16 hours

Sources & evidence

ORD record: ord-66ec71c51e90449bbcc928a39446ce0f
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09393220B2

Linked notes

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