Hydrochloric Acid → Mavacoxib

Participants

Reaction Conditions

Reaction Steps

The following procedure describes a method of preparing the crystal Form I of 4-[5-(4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-benzenesulfonamide without isolating the crystal Form II. 2-propanol (70 ml) and ethyl trifluoroacetate (27.15 g, 0.191 moles) are added to a first vessel, followed by a line wash of 2-propanol (10 ml). Next, 25% sodium methoxide in methanol (37.5 g, 0.174 moles) is added to the vessel, followed by a line wash of 2-propanol (10 ml). Next, 4-fluoroacetophenone (20 g, 0.145 moles) is added followed by a line wash of 2-propanol (10 ml). The contents of vessel are heated to 55° C. and held at that temperature for 2 hours, then cooled to ambient temperature. Water (110 ml), concentrated hydrochloric acid (20.0 g, 0.203 moles), and 4-sulfonamidophenylhydrazine hydrochloride (32.4 g, 0.145 moles) are added to a second vessel, followed by a line wash of water (10 ml). The contents of the first vessel are added to the second vessel, followed by a line wash of 2-propanol (60 ml). The combined contents are heated at 70° C. for 2 hours, then cooled to 55° C. and seeded with 10 mg (0.05% wt/wt relative to 4-fluoroacetophenone) of Form I of 4-[5-(4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-benzenesulfonamide. The contents are held at 55° C. for 6 hours, then cooled to ambient temperature and filtered. The product is washed with 50% aqueous 2-propanol (120 ml) and water (60 ml), then dried under vacuum at 55° C. to give 4-[5-(4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-benzenesulfonamide of the desired Form I polymorph (44.8 g, 80%).

Provenance & Evidence