Lithium Hydroxide → HCID 86719444, compound

Participants

Reaction Steps

To a stirred solution of methyl 2-((4S,5S)-1-(3-bromo-4-(((3R,4R)-1-(5-chloro-2-methoxypyridin-4-yl)-3-methylpiperidin-4-yl)oxy)phenyl)-4-methyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-5-yl)acetate (44 mg, 0.069 mmol) in THF (2.0 mL) and water (0.2 mL) at rt was added 1.0M aqueous lithium hydroxide (0.2 mL, 0.200 mmol). After stirring at rt for 4.5 h, the reaction mixture was partially evaporated to remove most of the THF. The remaining solution was partitioned between water (50 mL) and Hex (15 mL). The aqueous layer was acidified to pH 2 by dropwise addition of 1M HCl, and then extracted with CH2Cl2 (3×30 mL). The combined organic extracts were dried (Na2SO4) and concentrated. The residue was dried under vacuum to afford 2-((4S,5S)-1-(3-bromo-4-(((3R,4R)-1-(5-chloro-2-methoxypyridin-4-yl)-3-methylpiperidin-4-yl)oxy)phenyl)-4-methyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-5-yl)acetic acid (43 mg, 100% yield) as a white solid: LC-MS [M+H] 619, 621. 1H NMR (500 MHz, CD2Cl2) δ 7.97 (s, 1H), 7.36 (d, J=2.8 Hz, 1H), 7.02 (dd, J=9.0, 2.8 Hz, 1H), 6.95 (d, J=9.0 Hz, 1H), 6.30 (s, 1H), 4.41 (m, 1H), 4.02 (dt, J=3.9, 8.3 Hz, 1H), 3.86 (s, 3H), 3.54 (m, 2H), 3.28 (m, 1H), 2.90 (m, 1H), 2.84 (dd, J=16.5, 3.1 Hz, 1H), 2.18 (m, 2H), 1.86 (m, 2H), 1.35 (d, J=7.1 Hz, 3H), 1.17 (d, J=6.7 Hz, 3H). Analytical HPLC (Zorbax method, 50% Solvent B start): RT=8.55 min, HI: 100%. hGPR40 EC50=45 nM.

Provenance & Evidence