Sulfuric Acid → (R)-3-cyclopentyl-2-(4-cyclopropylsulfanyl-phenyl)-propionic acid

Participants

Reaction Conditions

Reaction Steps

A solution of (R)-3-cyclopentyl-2-(4-cyclopropylsulfanyl-phenyl)-N-((1R,2R)-2-hydroxy-1-methyl-2-phenyl-ethyl)-N-methyl-propionamide (715 mg, 1.63 mmol) in dioxane (5 mL) was treated with a 9 N aqueous sulfuric acid solution (1.3 mL). The resulting solution was then heated at 105° C. for 16 h. The reaction was then cooled and diluted with water (13 mL) and extracted with a chloroform/methanol solution (3:2, 3×20 mL) and then combined the organic extracts dried over magnesium sulfate, filtered and concentrated. Purification on an AnaLogix Intelliflash system (12 g column, 10% ethyl acetate/hexanes to 80% ethyl acetate/hexanes) afforded (R)-3-cyclopentyl-2-(4-cyclopropylsulfanyl-phenyl)-propionic acid (278 mg, 59%) as a white solid: [α]25589=−52.6° (c=0.19, methanol); ES-HRMS m/e calcd for C17H22O2S (M−H)− 289.1268, observed 289.1268; 1H NMR (300 MHz, CDCl3) δ 1.61-2.05 (m, 4H, 2×CH2), 2.45 (s, 3 H, ArCH3), 3.76 (m, 2H, OCH2), 4.00 (m, 2H, SO3CH2), 4.08 (m, 1H, OCH), 7.35 (brd, 2H, Ar), 7.81 (brd, 2H, Ar).

Provenance & Evidence