Hydrochloric Acid → (S)-4-((3S,4S)-3-fluoro-1-((R)-1-(4-methylbenzyl)-2-oxopyrrolidin-3-yl)piperidin-4-yl)phenyl 2-amino-3-methylbutanoate hydrochloride

Participants

Reaction Steps

To a solution of (S)-4-((3S,4S)-3-fluoro-1-((R)-1-(4-methylbenzyl)-2-oxopyrrolidin-3-yl)piperidin-4-yl)phenyl 2-((tert-butoxycarbonyl)amino)-3-methylbutanoate (0.025 g, 0.043 mmol) in DCM (1.5 mL) at −20° C. was added HCl in diethyl ether (2.5 ml, 2.50 mmol, 1.0 M). The reaction mixture was slowly warmed to rt over 10 min and then allowed to stir at rt for 19 h. The solvent was then removed in vacuo to provide a pale yellow semisolid. The crude product was then purified by RP-HPLC on a Sunfire C18 (250×20 mm) 5 μm column using a gradient of 10% solvent B to 75% solvent B over 12 minutes at 15 mL/min where solvent A=0.05% HCl in water and solvent B=acetonitrile. Active fractions were concentrated by lyophilization to provide 10.2 mg (44%) of (S)-4-((3S,4S)-3-fluoro-1-((R)-1-(4-methylbenzyl)-2-oxopyrrolidin-3-yl)piperidin-4-yl)phenyl 2-amino-3-methylbutanoate hydrochloride, the titled compound of example 2 as an off-white solid. LC-MS (Method A) RT=2.20 min, (M+H)+=482.2. 1H NMR: (400 MHz, DMSO-d6) δ ppm 8.64-8.78 (m, 3H) 7.38-7.46 (m, 2H) 7.23 (d, J=8.53 Hz, 2H) 7.18 (s, 4H) 5.04-5.26 (m, 1H) 4.42 (d, J=9.54 Hz, 3H) 4.17-4.23 (m, 2H) 3.29-3.40 (m, 4H) 3.19-3.28 (m, 2H) 2.30 (s, 6H) 2.04-2.19 (m, 2H) 1.11 (dd, J=12.55, 7.03 Hz, 6H). 19F NMR (376 MHz, DMSO-d6) δ −183.904.

Provenance & Evidence