Hydrochloric Acid → Duloxetine Hydrochloride

HRID 2060931Notes

Reaction equation

HRID 2060931 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.[ClH:22]>C(OCC)(=O)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]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 60835Duloxetine

Product 1

HCID 60834Duloxetine Hydrochloride

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Sodium hydroxide solution (30% w/v; 150 ml) was added to a stirred suspension of duloxetine maleate (200 g, 0.484 mole) in a mixture of toluene (2.0 L) and deionised water (2.0 L) at about 25° C. to attain a pH of 11 to 12. The mixture was stirred for 10 minutes. Toluene layer was separated and aqueous layer was extracted with toluene (1.0 L). The combined toluene layer was washed with deionised water (2×1.0 L) and concentrated under vacuum to obtain duloxetine free base as an oily mass. The duloxetine free base so obtained was stirred in ethyl acetate (1.0 L) and ethanolic hydrochloric acid (65.46 g; 0.484 mole; 27% w/w; 1.0 mole equivalent) was added to the stirred solution at 15° to 20° C. The mixture was stirred at 15° to 20° C. for 30 minutes, at 20° to 25° C. for 2 hours and subsequently at 5° to 10° C. for 2 hours. The solid was filtered and subjected to running wash with ethyl acetate (1×200 ml) followed by slurry wash with ethyl acetate (2×400 ml) till the pH of the filtrate attains the range of 5 to 6. The solid so obtained was dried under vacuum at 40° to 45° C. to obtain the title compound as an off-white solid.

Workup

  1. filtrationThe solid was filtered
  2. washto running wash with ethyl acetate (1×200 ml)
  3. washwash with ethyl acetate (2×400 ml) till the pH of the filtrate
  4. customThe solid so obtained
  5. customwas dried under vacuum at 40° to 45° C.

Sources & evidence

ORD record
ord-5f7318d849ef4e0687305dfb464fdaca
Source dataset
uspto-grants-2012_10
Patent number
US08278463B2

Reaction notes

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