Ammonium Chloride → Ethyl 2-(methylthio)pyrimidine-5-carboxylate

Temperature

80 °C

Ethyl 4-chloro-2-methylthio-5-pyrimidine carboxylate (12.5 g, 53.88 mmol) and Zn powder (14.1 g, 215.52 mmol) were combined and benzene (60 ml) and 3M NH4Cl (140 ml) were added. The suspension was stirred vigorously and heated to 80° C. for 30 h. The reaction mixture was filtered through celite and washed with EtOAc (200 ml). The filtrate was concentrated in vacuo to about 50 ml and then partitioned between H2O (400 ml) and EtOAc (400 ml). The aqueous layer was further extracted with EtOAc (250 ml). The combined organic layers were dried (MgSO4) and concentrated in vacuo to a dark oil. This was purified by column chromatography eluting with neat heptane followed by 1:1:1 heptane/CH2Cl2/Et2O and finally 2:2:0.5 heptane/CH2Cl2/Et2O. The title compound was obtained as a colourless oil (13 g, 61%). m/z 199 [M+H]+, 1H NMR (300 MHz, d6-DMSO) δ: 1.30 (3H, t), 2.60 (3H, s), 4.35 (2H, q), 9.0 (2H, s).

1. filtrationThe reaction mixture was filtered through celite
2. washwashed with EtOAc (200 ml)
3. concentrationThe filtrate was concentrated in vacuo to about 50 ml
4. custompartitioned between H2O (400 ml) and EtOAc (400 ml)
5. extractionThe aqueous layer was further extracted with EtOAc (250 ml)
6. dry with materialThe combined organic layers were dried (MgSO4)
7. concentrationconcentrated in vacuo to a dark oil
8. customThis was purified by column chromatography
9. washeluting with neat heptane

ORD record

ord-b3d2e732d58847778d0f34e256f7373a

Source dataset

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07932246B2