Water → Duloxetine

HRID 2060932Notes

Reaction equation

HRID 2060932 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; 15.5 ml) was added to a stirred suspension of duloxetine maleate (20 g, 0.0484 mole) in a mixture of toluene (200 ml) and deionised water (200 ml) at 15° to 20° C. to attain a pH of 12. The mixture was stirred for 10 minutes. Toluene layer was separated and aqueous layer was extracted with toluene (100 ml). The combined toluene layer was washed with deionised water (2×100 ml) and concentrated under vacuum to obtain duloxetine free base as an oily mass. The duloxetine free base so obtained was stirred in ethyl acetate (140 ml) and ethanolic hydrochloric acid (8.52 g; 0.063 mole; 27% w/w; 1.3 mole equivalent) at 10° to 15° C. The mixture was stirred at 10° to 15° C. for 30 minutes and subsequently at 20° to 25° C. for 3 hours. The reaction mixture was divided into two parts namely Part A and Part B.

Workup

  1. customToluene layer was separated
  2. extractionaqueous layer was extracted with toluene (100 ml)
  3. washThe combined toluene layer was washed with deionised water (2×100 ml)
  4. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-b6d9af712b27414ea7ed86e51e1a60c5
Source dataset
uspto-grants-2012_10
Patent number
US08278463B2

Reaction notes

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