Iodine → 2-Chloro-5-fluoro-4-isopropyl-pyrimidine

Temperature

0 °C

A stirred solution of 5-fluoro-2-chloropyrimidine (5.00 g, 37.7 mmol) in 1,2-dimethoxyethane (25 mL) is reacted with a solution of 2 M isopropyl magnesium chloride in tetrahydrofuran (28.3 mL, 56.6 mmol) while keeping the temperature below 15° C. The resulting solution is stirred for one hour under nitrogen and then cooled to 0° C. Triethylamine (5.76 mL, 37.7 mmol) in tetrahydrofuran (5 mL) is added followed by a solution of iodine (9.58 g, 37.7 mmol) in tetrahydrofuran (20 mL). After the addition is complete the dark reaction mixture is quenched with water followed by saturated sodium bicarbonate and saturated sodium bisulfate. The mixture is extracted with ethyl acetate (3×). The combined organic layers are dried over sodium sulfate and the solvent is removed under reduced pressure. The resulting residue is purified by silica gel column chromatography using a 5-100% gradient of dichloromethane in hexanes to give the title compound (2.55 g, 39%). GC/MS (m/e): 174.

1. customthe temperature below 15° C
2. additionAfter the addition
3. customthe dark reaction mixture
4. customis quenched with water
5. extractionThe mixture is extracted with ethyl acetate (3×)
6. dry with materialThe combined organic layers are dried over sodium sulfate
7. customthe solvent is removed under reduced pressure
8. customThe resulting residue is purified by silica gel column chromatography

ORD record

ord-39bd3df167374c64a2ab759d952e0d03

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09328124B2