Triphenylphosphine → t-butyl-(S)-2-(2-(3-trifluoromethylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxy)propanate

Participants

Reaction Conditions

Reaction Steps

A solution of N-(3-(3-trifluoromethylphenyl)-4-hydroxybenzyl)-4-fluoro-N-methylbenzenesulfonamide (36) (50.0 mg, 0.114 mmol) and (R)-t-butyl-2-hydroxypropanoate (18.3 mg, 0.125 mmol, 1.1 eq, Chem-Impex International, Inc., Wood Dale, Ill., USA) in THF (2 mL) at 0° C. was added diethyl azodicarboxylate (20 μL, 0.125 mmol, 1.1 eq) and triphenylphosphine (33 mg 0.125 mmol, 1.1 eq). After stirring at 0° C. for 4 h the mixture was extracted between saturated sodium bicarbonate and ethyl acetate, dried (Na2SO4) and concentrated in vacuo. This crude product was purified on reversed phase semi-preparative HPLC to give 9 mg of t-butyl-(S)-2-(2-(3-trifluoromethylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxy)propanate. This intermediate was then dissolved in TFA/DCM (1 mL/1 mL) and stirred at room temperature for 30 min. Solvent was removed in vacuo and the residue was purified via reversed phase semi-preparative HPLC to afford 4.9 mg of (S)-2-(2-(3-trifluoromethylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxy)propanoic acid (Example 36). 1HNMR (CDCl3, 400 MHz): δ 7.84 (m, 3H), 7.70 (d, 1H), 7.56 (m, 2H), 7.26 (m, 3H), 7.20 (d, 1H), 6.88 (d, 1H), 4.80 (m, 1H), 4.15 (s, 2H), 2.64 (s, 3H), 1.57 (d, 3H). MS (ESI): MH+=512.1. HPLC (Method B) tR=2.78 min.

Provenance & Evidence