Ethylene Glycol → 2-{[6-(1,4-Dioxaspiro[4.5]dec-8-yloxy)-2-(trifluoromethyl)pyrimidin-4-yl]oxy}ethanol

Participants

Reaction Conditions

Reaction Steps

1,2-Ethanediol (60 μL, 1.1 mmol) and 4-chloro-6-(1,4-dioxaspiro[4.5]dec-8-yloxy)-2-(trifluoromethyl)pyrimidine (described in Example 1, Step 1) (91 mg, 0.27 mmol) were dissolved in tetrahydrofuran (1.4 mL) and cooled to 0° C. Sodium hydride (60%/mineral oil, 22 mg, 0.56 mmol) was added and stirred for 30 minutes at 0° C., then at 22° C. for 20 hours. LCMS analysis showed no remaining starting material, and as the main component, formation of the product, M+H 365. The reaction was quenched with aqueous bicarbonate. The aqueous solution was extracted with ethyl acetate and the organic extracts were washed with water, saturated NaCl, dried (Na2SO4) and the solvent removed in vacuo. The product was purified by preparative LCMS using a Waters Fraction-Linx instrument and a 30 mm×100 mm Sunfire C18 column; 38% CH3CN—H2O (0.1% TFA), 0.5 min, 4.5 min gradient to 56%; 60 mL/min; detector set at M+H 365; retention time, 5.7 min. HPLC found the UVmax as 240 nm. The solvent was removed by rotary evaporation to give 56 mg of product (57% yield). The compound of Example 56 was then obtained by following the steps described for Example 45.

Provenance & Evidence