methyl 5-(4-amino-2,5-dimethylphenoxy)-2,2-dimethylpentanoate

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-(4-Amino-2,5-dimethylphenoxy)-2,2-dimethylpentanoic acid, methyl ester as the free base (Example 2) (4.15 g, 15 mmol) in 50 mL of toluene, 2.33 g (15 mmol) of 2,4-difluorophenyl isocyanate is added and the solution is stirred at 50° C. for 18 hours overnight. The solid mixture is evaporated on a rotary evaporator; the precipitate is taken up in acetonitrile, treated with charcoal, filtered, evaporated, and the residual, crystalline precipitate is recrystallized from 70 mL of toluene: 50 mL of isooctane to afford 5.7 g of the title compound as a slight pink solid; mp 152°-153° C. The solid mixture is evaporated on a rotary evaporator treated with charcoal filtered evaporated the residual, crystalline precipitate is recrystallized from 70 mL of toluene

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 2.2 g (12.5 mmol) of para-methoxybenzenesulfonyl chloride in 10 mL of tetrahydrofuran is added over 10 minutes at 0° C. to a solution of 3.5 g (12.5 mmol) of 5-(4-amino-2,5-dimethylphenoxy)-2,2-dimethylpentanoic acid, methyl ester as the free base (Example 2) and 2.5 g (2×12.5 mmol) of triethylamine in 40 mL of tetrahydrofuran. The ice bath is removed and the solution is permitted to stir at ambient temperature for 24 hours. The triethylammonium chloride is removed by filtration, the solvent is removed; the residue is taken up in diethyl ether, and the solution washed with 2×25 mL of 2N hydrochloric acid solution, brine, dried (magnesium sulfate), and evaporated leaving 5.0 g of a colored oil which crystallizes on standing. Recrystallization from 35 mL of isopropyl ether in the presence of charcoal affords 3.3 g of the title compound as off-white crystals; mp 90°-92° C. The ice bath is removed The triethylammonium chloride is removed by filtration the solvent is removed the solution washed with 2×25 mL of 2N hydrochloric acid solution, brine dried (magnesium sulfate) evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 2.8 g (10 mmol) of 5-(4-amino-2,5-dimethylphenoxy)-2,2-dimethylpentanoic acid, methyl ester as the free base (Example 2) and 1.5 g (10 mmol) of phthalic anhydride in 100 mL of toluene is stirred at reflux beneath a phase separating head for 2 hours. The solvent is removed and on standing a red brown oil crystallizes. Recrystallization from isoctaneisopropyl ether with the addition of charcoal affords 2.8 g of the title compound as pale pink crystals; mp 109°-111° C. at reflux beneath a phase separating head for 2 hours The solvent is removed crystallizes Recrystallization from isoctaneisopropyl ether with the addition of charcoal