2,4-Dichloro-5-fluoropyrimidine → 2-Chloro-5-fluoro-4-methylpyrimidine

Temperature

0 °C

A solution of 2,4-dichloro-5-fluoropyrimidine (2.5 g, 14.97 mmol) and iron(III) acetylacetonate (1.058 g, 2.99 mmol) in THF (100 mL) and NMP (10 mL) was chilled below 0° C. and methyl magnesium chloride (5.99 mL, 18.0 mmol, 3.0 M solution in THF) was added dropwise over 10 minutes. After stirring for 2 hours at 0° C., the mixture was quenched with 200 mL saturated NH4Cl and extracted twice with 200 mL EtOAc. The combined organic extracts were washed with 200 mL saturated NH4Cl and 200 mL brine, dried over Na2SO4 and concentrated. Purification by chromatography (Grace Reveleris 80 g column, eluted with 0-20% EtOAc/heptane, 35 mL/min) provided the title compound (1.13 g, 7.70 mmol, 51% yield). GC/MS (EI+) m/z 146.0 (M+); 1H NMR (400 MHz, CDCl3) δ 8.36 (s, 1H), 2.55 (d, J=2.5, 3H); 13C NMR (101 MHz, CDCl3) δ 158.78, 158.61, 157.34, 154.92, 154.89, 154.74, 145.86, 145.63, 17.74, 17.73.

1. customthe mixture was quenched with 200 mL saturated NH4Cl
2. extractionextracted twice with 200 mL EtOAc
3. washThe combined organic extracts were washed with 200 mL saturated NH4Cl and 200 mL brine
4. dry with materialdried over Na2SO4
5. concentrationconcentrated
6. customPurification
7. washby chromatography (Grace Reveleris 80 g column, eluted with 0-20% EtOAc/heptane, 35 mL/min)

ORD record

ord-2fda4aafd2864521beeca746a19b3dce

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09012651B2