Hydrochloric Acid → Duloxetine Hydrochloride

HRID 222780

Reaktionsgleichung

Reaktionsgleichung von HRID 222780
[CH3:1][NH:2][CH2:3][CH2:4][C@H:5]([O:11][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=12)[C:6]1[S:10][CH:9]=[CH:8][CH:7]=1.[ClH:22].C(C(C)=O)C>C(OC(=O)C)C>[CH3:1][NH:2][CH2:3][CH2:4][C@H:5]([O:11][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=12)[C:6]1[S:10][CH:9]=[CH:8][CH:7]=1.[ClH:22]

Komponenten

5

Edukt 3

HCID 313Hydrochloric AcidHCID 6569Methyl Ethyl KetoneHCID 60835Duloxetine2×

Produkt 1

HCID 60834Duloxetine Hydrochloride

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8857Ethyl AcetateLösungsmittel2×

Versuchsvorschrift

A method of preparation of the hydrochloride salt from the duloxetine base represents another aspect of the present invention. Preparation of this salt is commonly performed via reaction of the duloxetine base with concentrated hydrochloric acid in ethylacetate environment. However, it has now turned out that substitution of ethylacetate by a lower ketone, such as for example ethylmethylketone, results in higher yields of higher quality duloxetine hydrochloride, especially when duloxetine hydrochloride is prepared and isolated via the method according to this invention. For comparison of effects of the used solvent on quality of the substance, we have used contaminated duloxetine hydrochloride that was obtained as the second fraction from mother liquors after their concentration. In Table 1, a HPLC print-out (C18 reverse column, mobile phase: water/acetonitrile, phosphate buffer pH 7.6) is presented showing analysis of the starting substance and then of the purified substance obtained after 1 hour refluxing in a six-fold amount of the solvent (i.e. 6 ml of the solvent for 1 g of the starting substance), cooling to ambient temperature, filtration and drying.

Aufarbeitung

  1. customPreparation of this salt
  2. customresults

Quellen und Nachweise

ORD-Eintrag
ord-27f361676e984e9f9440f93773199df7
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08207356B2

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