Tolmetin → HCID 131730794, compound

HRID 1525581Notes

Reaction equation

HRID 1525581 reaction equation
C(OC(C)C)(C)C.[CH3:8][NH:9][CH2:10][CH2:11][C@H:12]([O:18][C:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=[CH:21][CH:20]=1)[C:13]1[S:17][CH:16]=[CH:15][CH:14]=1.[CH3:29][C:30]1[CH:31]=[CH:32][C:33]([C:36]([C:38]2[N:42]([CH3:43])[C:41]([CH2:44][C:45]([OH:47])=[O:46])=[CH:40][CH:39]=2)=[O:37])=[CH:34][CH:35]=1>C(OCC)(=O)C>[CH3:8][NH:9][CH2:10][CH2:11][C@H:12]([O:18][C:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=[CH:21][CH:20]=1)[C:13]1[S:17][CH:16]=[CH:15][CH:14]=1.[CH3:29][C:30]1[CH:31]=[CH:32][C:33]([C:36]([C:38]2[N:42]([CH3:43])[C:41]([CH2:44][C:45]([OH:47])=[O:46])=[CH:40][CH:39]=2)=[O:37])=[CH:34][CH:35]=1

Participants

5

Reactant 3

HCID 5509TolmetinHCID 7914Diisopropyl EtherHCID 60835Duloxetine

Product 1

HCID 131730794HCID 131730794, compoundYield 130.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

Diisopropyl ether was added drop wise to a solution of (S)-duloxetine (289 mg, 0.97 mmol) and tolmetin (500 mg, 1.94 mmol, 2 eq) in ethyl acetate (1 mL) at reflux until precipitation started. Following, the minimum amount of ethyl acetate was added drop wise to reach complete dissolution again. The solution was then cooled to room temperature, and slowly stirred during 48 h. The resulting suspension was filtered off, washed with cold ethyl acetate and dried under vacuum (10 mm Hg) at 40° C. for 4 hours to give a solid corresponding to a 1:2 ratio (S)-duloxetine-tolmetin co-crystal (700 mg, 89% yield).

Workup

  1. temperatureat reflux until precipitation
  2. dissolutiondissolution again
  3. filtrationThe resulting suspension was filtered off
  4. washwashed with cold ethyl acetate
  5. customdried under vacuum (10 mm Hg) at 40° C. for 4 hours

Sources & evidence

ORD record
ord-0ca192f4d1fc4d759f1077fb9a73c376
Source dataset
uspto-grants-2015_07
Patent number
US09084774B2

Reaction notes

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