ethyl 2-[4-(aminomethyl)phenoxy]-2-methylpropanoate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 0.16 g (0.68 mmol) of 2-(4-aminomethyl-phenoxy)-2-methyl-propionic acid ethyl ester [PCT Int. Appl. WO 2002/096895 A1] and 0.16 g (0.62 mmol) of 5-(4-trifluoromethoxy-phenyl)-pent-4-ynoic acid (example 29D]) were dissolved in 4 ml of dichloromethane. This solution was cooled to 0° C. and then 0.14 g (0.74 mmol) of N-(3-dimethylamino-propyl)-N′-ethyl-carbodiimide-hydrochloride was added and the reaction stirred for 28 hours at ambient temperature. It was subsequently poured into aqueous 10% KHSO4/ether and extracted two fold with ether; the organic layers were washed with aqueous saturated NaHCO3, dried (Na2SO4), filtered and evaporated. The crude product was purified by flash chromatography (SiO2; n-heptane/AcOEt=9:1 to 1:2) to give 0.14 g of the title compound as light brown oil. extracted two fold with ether the organic layers were washed with aqueous saturated NaHCO3 dried (Na2SO4) filtered evaporated The crude product was purified by flash chromatography (SiO2; n-heptane/AcOEt=9:1 to 1:2)

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: In analogy to the procedures described in example 26B] and 26C, 2-(4-aminomethyl-phenoxy)-2-methyl-propionic acid ethyl ester [PCT Int. Appl. (2002), WO 2002/096895A1] was reacted with 4-trifluoromethyl-2-(4-trifluoromethyl-phenyl)-pyrimidine-5-carboxylic acid (prepared by saponification from 4-trifluoromethyl-2-(4-trifluoromethyl-phenyl)-pyrimidine-5-carboxylic acid ethyl ester (example 107B]) in analogy to example 53B]) to give 2-methyl-2-[4-({[4-trifluoromethyl-2-(4-trifluoromethyl-phenyl)-pyrimidine-5-carbonyl]-amino}-methyl)-phenoxy]-propionic acid ethyl ester, which was subsequently saponified to yield the title compound as colorless solid.