Ethyl formate → 5-(2,4-Difluorophenoxy)-2-methylsulfanylpyrimidin-4-ol

To a solution of 2-(2,4-difluorophenoxyl)acetic acid ethyl ester (8.0 g, 37.01 mmol) and ethyl formate (4.11 g, 55.51 mmol) in dry THF (200 mL) was added NaH (1.55 g, 38.75 mmol) slowly at 0° C. The mixture was then refluxed for 2 h. In a separate flask, sodium ethoxide (3.02 g, 44.41 mmol) and S-methylthiopseudourea hemisulfate (6.17 g, 44.41 mmol) in EtOH (100 mL) were stirred at 20° C. for 2 h and then the resulting mixture was added to the above THF solution. The combined mixture was refluxed for 12 h. After concentration under vacuum, water (20 mL) and HCl (10 mL, aq. 1N) were added. The suspended solids were collected and washed with water (50 mL×3) and EtOH (50 mL×3) and dried to give the title compound (6.0 g, 60.0% yield) as a light yellow solid. 1H NMR (DMSO-d6, 400 MHz) δ 7.84 (s, 1H), 7.42-7.34 (m, 1H), 7.04-7.01 (m, 1H), 6.95 (t, J=9.6 Hz, 1H), 2.47 (s, 3H). LCMS: 271.1 (M+1)+

1. temperatureThe mixture was then refluxed for 2 h
2. temperatureThe combined mixture was refluxed for 12 h
3. concentrationAfter concentration under vacuum, water (20 mL) and HCl (10 mL, aq. 1N)
4. additionwere added
5. customThe suspended solids were collected
6. washwashed with water (50 mL×3) and EtOH (50 mL×3)
7. customdried

ORD record

ord-7b8f3775189841e191d8dad421db2478

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09115114B2