Process for the preparation of nefazodone hydrochloride

A process for the preparation of Nefazodone Hydrochloride comprising

• (i) adding Semicarbazide of Formula 2 in methanol to hydrochloric acid in isopropanol;
• (ii) heating the mixture to reflux for about 2.5 to about 3.0 hours and subsequently cooling it to room temperature;
• (iii) filtering the reaction mixture and washing the solid with methanol and subsequently drying same under vacuum to afford of Semicarbazide Dihydrochloride of Formula 3;
• (iv) adding trimethylsilyl chloride slowly to a suspension of Semicarbazide Dihydrochloride in ethanol, followed by triethyl orthopropionate and stirring for 14-16 hours;
• (v) adding hydrochloric acid in isopropanol to the reaction mixture and stirring for 6-8 hours;
• (vi) adding trimethylsilyl chloride to the reaction mixture, followed by triethyl orthopropionate and stirring for 12-14 hours;
• (vii) adding hydrochloric acid in isopropanol to the reaction mixture and stirring for 2-3 hours;
• (viii) adding heptane to the reaction mixture and stirring for 2-3 hours and subsequently distilling of solvent mixture under reduced pressure and adding heptane and stirring for 4-6 hours;
• (ix) filtering the reaction mixture as a damp product and washing same with heptane and ethanol mixture (4:1) to afford crude Nefazodone Hydrochloride;

A process for the preparation of Nefazodone Hydrochloride comprising:

• (i) adding a predetermined amount of semicarbazide of Formula 2 in methanol to a predetermined amount of hydrochloric acid in isopropanol;
• (ii) heating the mixture to reflux for a predetermined time period and subsequently cooling it to room temperature;
• (iii) filtering the reaction mixture and washing the solid with methanol and subsequently drying same under vacuum to afford Semicarbazide Dihydrochloride of Formula 2;
• (iv) adding a predetermined amount of trimethylsilyl chloride slowly to a suspension of the Semicarbazide Dihydrochloride in ethanol, followed by a predetermined amount of triethyl orthopropionate and stirring for a predetermined period of time;
• (v) adding a predetermined amount of hydrochloric acid in isopropanol to the reaction mixture and stirring for a predetermined amount of time;
• (vi) adding a predetermined amount of trimethylsilyl chloride to the reaction mixture, followed by a predetermined amount of triethyl orthopropionate and stirring for a predetermined amount of time;
• (vii) adding a predetermined amount of hydrochloric acid in isopropanol to the reaction mixture and stirring for a predetermined amount of time;
• (viii) adding a predetermined amount of heptane to the reaction mixture and stirring for a predetermined amount of time and subsequently distilling a predetermined amount of solvent mixture under reduced pressure and adding heptane and stirring for a predetermined amount of;
• (ix) filtering the reaction mixture as a damp product and washing same with heptane and ethanol mixture (4:1) to afford crude Nefazodone Hydrochloride;

A process for the preparation of Nefazodone Hydrochloride comprising:

• (i) adding a predetermined amount of trimethylsilyl chloride slowly to a suspension of Semicarbazide Dihydrochloride of Formula 3 in ethanol, followed by addition of triethyl orthopropionate;
• (ii) adding hydrochloric acid in isopropanol to the reaction mixture and mixing;
• (iii) adding a predetermined amount of trimethylsilyl chloride to the reaction mixture, followed by triethyl orthopropionate;
• (iv) adding hydrochloric acid in isopropanol to the reaction mixture;
• (v) adding a predetermined amount of heptane to the reaction mixture and subsequently distilling a predetermined amount of solvent mixture under reduced pressure and adding heptane;
• (vi) filtering the reaction mixture as a damp product and washing same with for example heptane and ethanol mixture (4:1) to afford crude Nefazodone Hydrochloride;