Lithium Hydroxide → 2-(4-(5-(4-(Difluoromethoxy)phenyl)pyrimidin-2-ylamino)phenyl)-3-hydroxypropanoic acid

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To a solution of ethyl 2-(4-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)phenyl)-3-hydroxypropanoate 32 (1 mmol) in THF:MeOH:water (3:2:1 v/v) is added 6 N LiOH (3 mmol). The reaction mixture is stirred at rt for 1 h until complete by LC/MS and diluted with water. The aqueous layer is washed with DCM (2×30 mL) and acidified to pH=5 using aqueous 1N HCl. The resulting mixture is extracted with DCM (3×50 mL). The organic layer is separated, dried over Na2SO4 and concentrated to yield a crude product, which upon crystallization from water yield 2-(4-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)phenyl)-3-hydroxypropanoic acid, 26 as off white solid. 1H NMR (400 MHz, d6-DMSO) δ 9.65 (s, 1H), 8.79 (s, 2H), 7.76 (d, J=8.8 Hz, 2H), 7.60 (d, J=8.4 Hz, 2H), 7.30 (s, 1H), 7.27 (d, J=8.8 Hz, 2H), 7.17 (d, J=8.4 Hz, 2H), 3.60-3.70 (m, 2H), 3.50-3.58 (m, 2H), 3.20-3.26 (m, 2H). MS (m/z) (M+1)+: 402.1.

Provenance & Evidence