Sodium Hydroxide → Duloxetine

HRID 2060929Notes

Reaction equation

[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.Cl.[OH-].[Na+]>>[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

Participants

Reactant 2

HCID 14798Sodium Hydroxide

HCID 60834Duloxetine Hydrochloride

Product 1

HCID 60835DuloxetineYield 98.8%

Procedure

The duloxetine hydrochloride (5 g) obtained in step A) was treated with 1 N sodium hydroxide (0.72 g; 18 ml) and extracted with toluene (50 ml). The toluene layer was evaporated to obtain the free base of duloxetine (4.4 g). The free base of duloxetine was loaded on a silica gel column (dry slurry with 10 g of silica gel) with dichloromethane. The elution was started with 0.5% v/v of methanol in dichloromethane and the free base of duloxetine was eluted with 1% v/v methanol in dichloromethane, and the eluted fractions were concentrated under vacuum to obtain the free base of duloxetine. The impurity of Formula II was eluted with 10% v/v methanol in dichloromethane and the eluted fractions were concentrated under vacuum to obtain the title compound.

Workup

extractionextracted with toluene (50 ml)
customThe toluene layer was evaporated

Sources & evidence

ORD record: ord-659f62d384724b51a5ce76cab5bf29a2
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08278463B2

Reaction notes

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