Water → Duloxetine

HRID 2060930Notes

Reaction equation

HRID 2060930 reaction equation
[OH-].[Na+].[CH3:3][NH:4][CH2:5][CH2:6][C@H:7]([O:13][C:14]1[CH:15]=[CH:16][CH:17]=[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=12)[C:8]1[S:12][CH:11]=[CH:10][CH:9]=1.C([O-])(=O)/C=C\C([O-])=O.O>C1(C)C=CC=CC=1>[CH3:3][NH:4][CH2:5][CH2:6][C@H:7]([O:13][C:14]1[CH:15]=[CH:16][CH:17]=[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=12)[C:8]1[S:12][CH:11]=[CH:10][CH:9]=1

Participants

5

Reactant 3

HCID 962WaterHCID 14798Sodium HydroxideHCID 86635738HCID 86635738, compound

Product 1

HCID 60835Duloxetine

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

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. customToluene layer was separated
  2. extractionaqueous layer was extracted with toluene (1.0 L)
  3. washThe combined toluene layer was washed with deionised water (2×1.0 L)
  4. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-03558ae5063f42508885fcec653f298f
Source dataset
uspto-grants-2012_10
Patent number
US08278463B2

Reaction notes

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