Lithium hydroxide, monohydrate → (S)-2-(6-((S)-1,2-dihydroxyethyl)-2-(4-(4-fluorophenoxy)phenyl)pyrimidine-4-carboxamido) propanoic acid

To a solution of (S)-methyl 2-(6-((S)-1,2-dihydroxyethyl)-2-(4-(4-fluorophenoxy)phenyl)pyrimidine-4-carboxamido)propanoate (0.100 g, 0.22 mmol) in 5:1 THF/water (5 mL) was added LiOH.H2O (0.009 g, 0.21 mmol). After stirring overnight additional LiOH.H2O (0.001 g, 0.02 mmol) was added. After 5 hours the reaction was evaporated in vacuo. To the residue was added 5 mL water and 0.22 mL 1N HCl. The resulting precipitate was filtered off, washed with water, and dried under vacuum. The solid was triturated with 2 mL 20% EtOAc/hexanes, isolated, and rinsed with additional hexanes. The material was dried under vacuum to give (S)-2-(6-((S)-1,2-dihydroxyethyl)-2-(4-(4-fluorophenoxy)phenyl)pyrimidine-4-carboxamido) propanoic acid (Compound Example No. 15) as an off-white powder (0.062 g, 0.14 mmol, 64% yield). 1H NMR (400 MHz, DMSO-d6): 12.82 (1 H, s), 9.23 (1 H, d, J=7.9 Hz), 8.62 (2 H, d, J=9.0 Hz), 8.00 (1 H, s), 7.33-7.25 (2 H, m), 7.23-7.16 (2 H, m), 7.13 (2 H, d, J=8.8 Hz), 5.82 (1 H, d, J=5.3 Hz), 4.83 (1 H, t, J=5.9 Hz), 4.70 (1 H, q, J=4.4 Hz), 4.55 (1 H, p, J=7.5 Hz), 3.84-3.76 (1 H, m), 3.71-3.63 (1 H, m), 1.48 (3 H, d, J=7.2 Hz); LC/MS: m/z=442.1 [M+H]+.

1. additionwas added
2. customAfter 5 hours the reaction was evaporated in vacuo
3. additionTo the residue was added 5 mL water and 0.22 mL 1N HCl
4. filtrationThe resulting precipitate was filtered off
5. washwashed with water
6. customdried under vacuum
7. customThe solid was triturated with 2 mL 20% EtOAc/hexanes
8. customisolated
9. washrinsed with additional hexanes
10. customThe material was dried under vacuum

ORD record

ord-c7f32d0d049241b4bd2307371766964c

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09133131B2