Phosphorus oxychloride → (+/-)-2,4-Dichloro-5-(1-chloroethyl)-pyrimidine

Temperature

0 °C

To a solution of (±)-1-(2,4-dichloro-pyrimidin-5-yl)-ethanol (1.27 g, 6.60 mmol) (from Example 1a supra) in phosphorus oxychloride (5.0 mL, 53.11 mmol) (Aldrich), at 0° C., was added diisopropylethyl-amine (2.60 mL, 14.78 mmol) (Aldrich). The reaction was stirred at 0° C. for 5 minutes, at ambient temperature for 15 minutes and then at 115° C. for 3 hours. The reaction was cooled to room temperature, diluted with toluene (10 mL) and the mixture was then poured into ice (15 g). After stirring for 10 minutes, the layers were separated and the aqueous extract was back washed with toluene. The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and concentrated. Purification by flash chromatography (Biotage, 40M, 10:90 to 15:85 ethyl acetate-hexanes gradient) gave (±)-2,4-dichloro-5-(1-chloroethyl)-pyrimidine as an oil. (Yield 1.233 g; 88.3%).

1. waitat 115° C. for 3 hours
2. temperatureThe reaction was cooled to room temperature
3. stirringAfter stirring for 10 minutes
4. customthe layers were separated
5. extractionthe aqueous extract
6. washwas back washed with toluene
7. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. customPurification by flash chromatography (Biotage, 40M, 10:90 to 15:85 ethyl acetate-hexanes gradient)

ORD record

ord-ed9ec06b2bbe43fa9cdfbd2e97309a22

Source dataset

uspto-grants-2006_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07129351B2