Hydrochloric Acid → Hydrochloric Acid

HRID 1851728Notes

Reaction equation

HRID 1851728 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.[C:22]([Cl:25])(=O)C.[ClH:26].[OH-].[Na+]>C(O)(C)C.CC(C)=O>[ClH:25].[ClH:26].[CH3:1][NH:2][CH2:3][CH2:4][C@:5]([CH3:22])([O:11][C:12]1[C:17]2[C:16](=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:15]=[CH:14][CH:13]=1)[C:6]1[S:10][CH:9]=[CH:8][CH:7]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6367Acetyl chlorideHCID 14798Sodium HydroxideHCID 60835Duloxetine2×

Product 2

HCID 313Hydrochloric AcidHCID 89914372HCID 89914372, compound

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 3776IsopropanolSolvent3×

Conditions

Temperature
50 °C

Procedure

The crude wet duloxetine free base (205.0 g) and an acetone (anti-solvent)(600.0 g) were charged in a 4-neck round flask and heated to a temperature of 50° C. while stirring. To another 4-neck round flask, isopropyl alcohol (IPA) (200.0 g) was charged, and the temperature was set to about 0 to about 5° C. while stirring. Fresh hydrochloride was prepared by dropping acetyl chloride (48.0 g) slowly to the isopropyl alcohol solution and stirring the reaction for one hour at a temperature of about 15° C. to 20° C. Then, the fresh hydrochloric acid in isopropyl alcohol was added to the duloxetine free base solution slowly, and the pH value was controlled in a range from 5.5 to 7.5 with NaOH(aq). The temperature was set at 50° C., and the reaction was gradually cooled to 0° C.˜5° C. The reaction was stirred for another one hour at about 0° C.˜5° C., and after filtration, the purified duloxetine hydrochloride was produced. (190 g, 99% ee; purity; 98% by HPLC assay).

Workup

  1. customwas set to about 0 to about 5° C.
  2. stirringwhile stirring
  3. stirringstirring
  4. customthe reaction for one hour at a temperature of about 15° C. to 20° C
  5. customwas set at 50° C.
  6. temperaturethe reaction was gradually cooled to 0° C.˜5° C
  7. stirringThe reaction was stirred for another one hour at about 0° C.˜5° C.
  8. filtrationafter filtration

Sources & evidence

ORD record
ord-4e42278bded74f989236ab70427046a8
Source dataset
uspto-grants-2015_02
Patent number
US08957227B2

Reaction notes

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