2-Chlorobenzaldehyde → HCID 59834305, compound

Temperature

-78 °C

To a solution of 4-chloro-2-(methylthio)pyrimidine (Aldrich) (20 g, 124.51 mmol) in dry THF (300 mL) at −78° C. under argon was slowly added a solution of 2.0 M lithium diisopropyl amide, i.e., LDA, (109 mL, 1.75 eq) in THF via a cannula. After addition was complete, the resulting mixture was stirred at −78° C. for an additional 15 minutes, after which 2-chlorobenzaldehyde (Aldrich) (29.5 mL, 2.1 eq) was added dropwise via syringe. The reaction mixture was stirred for an additional 30 minutes at −78° C. and then quenched with saturated ammonium chloride solution. Ethyl acetate was added, the mixture was allowed to warm to room temperature, and the layers were partitioned and separated. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were washed with brine solution. The ethyl acetate layers were combined, dried over magnesium sulfate, filtered and concentrated to give the crude product as an oil. Purification using Flash Column Chromatography on Silica Gel, eluting with a gradient of 5%-20% ethyl acetate in hexanes gave the title compound (10.8 g, (M+H)+=301) as an orange-yellow semi-solid.

1. additionAfter addition
2. stirringThe reaction mixture was stirred for an additional 30 minutes at −78° C.
3. customquenched with saturated ammonium chloride solution
4. additionEthyl acetate was added
5. temperatureto warm to room temperature
6. customthe layers were partitioned
7. customseparated
8. extractionThe aqueous layer was extracted with ethyl acetate
9. washthe combined organic layers were washed with brine solution
10. dry with materialdried over magnesium sulfate
11. filtrationfiltered
12. concentrationconcentrated
13. customto give the crude product as an oil
14. customPurification
15. washeluting with a gradient of 5%-20% ethyl acetate in hexanes

ORD record

ord-0fd3047df3a648cba0d79d6f75683ce1

Source dataset

uspto-grants-2009_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07566708B2