Preparation of sufentanil citrate and sufentanil base

Patent metadata

Field	Value
Publication number	US-10227335-B2
Application number	US-201615164483-A
Country	US
Kind code	B2
Filing date	May 25, 2016
Priority date	May 27, 2015
Publication date	Mar 12, 2019
Grant date	Mar 12, 2019

Abstract

Provided herein are processes for forming sufentanil citrate from sufentanil base. One process comprises forming sufentanil citrate in the presence of a polar non-aqueous solvent. Other processes comprise forming sufentanil citrate in the presence of water.

First claim

What is claimed is:

1. A process for preparing sufentanil citrate from sufentanil base, the process comprising:
(a) forming a reaction mixture comprising sufentanil base, citric acid, and isopropyl alcohol;
(b) heating the reaction mixture to a temperature of 70° C. to 90° C. to form a solution comprising sufentanil citrate;
(c) cooling the solution comprising sufentanil citrate to 50° C. to 70° C., seeding with crystals of sufentanil citrate, and maintaining the temperature at 50° C. to 60° C. thereby forming a slurry, the slurry comprising solid sufentanil citrate; and
(d) maintaining the temperature of the slurry at 50° C. to 60° C. and filtering the slurry at 50° C. to 60° C. to recover the solid sufentanil citrate, which contains less than about 2000 ppm of isopropyl alcohol.

2. The process of claim 1 , further comprising:
(e) contacting the mixture remaining after recovery of solid sufentanil citrate with a proton acceptor to form a sufentanil base mixture;
(f) cooling the sufentanil base mixture to form solid sufentanil base; and
(g) recovering solid sufentanil base.

3. The process of claim 2 , further comprising contacting solid sufentanil base from step (g) with a non-polar solvent to form a mixture, heating the mixture to dissolve the sufentanil base, and cooling the mixture to form crystalline sufentanil base.

4. The process of claim 3 , wherein the proton acceptor comprises a hydroxide and the non-polar solvent is an alkane.

Assignees

• Mallinckrodt Llc
• SpecGx LLC

Inventors

• Klemm George Helmut
• Orr Brian
• Mcclenaghan Joel

Classifications

• C07C51/412

  by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part · CPC title

• C07D409/06 Primary

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• C07C59/265

  Citric acid · CPC title