Ammonia → Duloxetine Hydrochloride

HRID 1811467Notes

Reaction equation

HRID 1811467 reaction equation
C(O)(=O)C(O)=O.[CH3:7][NH:8][CH2:9][CH2:10][C@H:11]([O:17][C:18]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:21]=[CH:20][CH:19]=1)[C:12]1[S:13][CH:14]=[CH:15][CH:16]=1.O.N.[ClH:30].C(OCC)(=O)C>C(Cl)Cl>[ClH:30].[CH3:7][NH:8][CH2:9][CH2:10][C@H:11]([O:17][C:18]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:21]=[CH:20][CH:19]=1)[C:12]1[S:13][CH:14]=[CH:15][CH:16]=1

Participants

6

Reactant 4

HCID 222AmmoniaHCID 962WaterHCID 11639633HCID 11639633, compoundHCID 21866389Hydrogen chloride-ethyl acetate

Product 1

HCID 60834Duloxetine Hydrochloride

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
2.5 °C

Procedure

A solution of 100 Kgs. of (S)-(+)-N-methyl-3-(1-naphthalenyloxy)-3-(2-thienyl) propanamine oxalate, 400 liters of water and 400 liters of methylene chloride is cooled to 0-5° C. Adjusted the pH of the reaction mixture 8.8 with aqueous ammonia. Stirred the reaction mixture for 15 minutes. Separated the organic layer and washed the organic phase with water. Distilled the solvent completely under reduced pressure at below 40° C. Added 400 liters of ethyl acetate to the above obtained crude. Cooled the reaction mixture to 0-5° C. Adjusted the pH of the reaction mixture to 2.0 with ethyl acetate HCl. Stirred the reaction mixture for 2 hours. Filtered the precipitated solid and washed with ethyl acetate. Dried the material at 45-50° C. to get the title compound.

Workup

  1. customSeparated the organic layer
  2. washwashed the organic phase with water
  3. distillationDistilled the solvent completely under reduced pressure at below 40° C
  4. additionAdded 400 liters of ethyl acetate to the
  5. customabove obtained crude
  6. stirringStirred the reaction mixture for 2 hours
  7. filtrationFiltered the precipitated solid
  8. washwashed with ethyl acetate
  9. customDried the material at 45-50° C.

Sources & evidence

ORD record
ord-3ccfb84fcb3a44909fd8dfd4cd866576
Source dataset
uspto-grants-2013_01
Patent number
US08362279B2

Reaction notes

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