Hydrochloric Acid → (2R)-2-(4-chloropyrazol-1-yl)propanoic acid

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(R)-Methyl 2-(4-chloro-1H-pyrazol-1-yl)propanoate (1.00 g, 5.30 mmol) was suspended in a solution of aqueous hydrochloric acid (6M, 8.8 mL, 53 mmol). The reaction mixture was stirred for 18 h at reflux. The mixture was cooled to 0° C. and quenched with a saturated aqueous solution of sodium phosphate (NaH2PO4). The pH was adjusted to 1-2 using aqueous sodium hydroxide and hydrochloric acid. The mixture was extracted with ethyl acetate (20 mL×3). The combined organics were washed with brine, dried over magnesium sulfate, filtered and concentrated. The residue was dried under vacuum, dissolved in a hot solution of heptanes:ethyl acetate (3:1, 9 mL) and allowed to cool to room temperature. A seed crystal was added while cooling. The mixture was stirred for 18 h. The solids were collected by filtration and washed with a solution of heptanes:ethyl acetate (3:1, 2 mL×2) and heptanes (2 mL×2). The resulting solids were air dried to afford (R)-2-(4-chloro-1H-pyrazol-1-yl)propanoic acid (310 mg, 33%). 1H NMR (500 MHz, CDCl3) δ 1.8 (d, 3H), 5.13 (q, 1H), 7.51 (s, 1H), 7.55 (s, 1H), 11.8 (s, 1H); MS (EI+) (M+) 174; Chiral HPLC retention time: 3.81 min (Method: Chiralpak AD-H 0.46×25 cm, Mobile Phase: 90/10 CO2/methanol; Flow: 2.5 mL/min); >99.5% ee.