Isopropanol → (S)-methyl 2-(6-((S)-1,2-dihydroxyethyl)-2-(4-(4-fluorophenoxy)phenyl) pyrimidine-4-carboxamido)propanoate

To a warmed milky suspension of (S)-methyl 2-(2-(4-(4-fluorophenoxy)phenyl)-6-vinylpyrimidine-4-carboxamido)propanoate (0,407 g, 0.966 mmol) in iPrOH (5 mL) and water (5 mL) was added AD-Mix-α (1.328 g). After stirring 2.5 hours the reaction mixture was partitioned between 25 mL water and 50 mL EtOAc. The organic layers were isolated and the aqueous layer extracted once more with 25 mL EtOAc. The combined organic layers were dried over Na2SO4, filtered, and evaporated in vacuo. The residue was chromatographed over silica gel using 50-100% EtOAc in hexanes. The product fractions were evaporated in vacuo to give (S)-methyl 2-(6-((S)-1,2-dihydroxyethyl)-2-(4-(4-fluorophenoxy)phenyl)pyrimidine-4-carboxamido)propanoate (Compound Example No. 14) as a cream-colored solid (0.236 g, 0.518 mmol, 54% yield). 1H NMR (400 MHz, DMSO-d6): 9.39 (1 H, d, J=7.9 Hz), 8.64 (2 H, d, J=9.0 Hz), 8.00 (1 H, s), 7.33-7.25 (2 H, m), 7.22-7.16 (2 H, m), 7.13 (2 H, d, J=9.0 Hz), 5.82 (1 H, d, J=5.3 Hz), 4.83 (1 H, t, J=6.1 Hz), 4.72-4.60 (2 H, m), 3.85-3.77 (1 H, m), 3.72-3.63 (4 H, m), 1.49 (3 H, d, J=7.2 Hz); LC/MS: m/z=456.1 [M+H]+.

1. customwas partitioned between 25 mL water and 50 mL EtOAc
2. customThe organic layers were isolated
3. extractionthe aqueous layer extracted once more with 25 mL EtOAc
4. dry with materialThe combined organic layers were dried over Na2SO4
5. filtrationfiltered
6. customevaporated in vacuo
7. customThe residue was chromatographed over silica gel using 50-100% EtOAc in hexanes
8. customThe product fractions were evaporated in vacuo

ORD record

ord-e40b778bed4043b7b85763a10a815085

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09133131B2