2-Chlorobenzaldehyde → (2-Chlorophenyl)-(4,6-dichloro-2-methylsulfanylpyrimidin-5-yl)-methanol

Temperature

-78 °C

To a solution of 4,6-dichloro-2-(methylthio)pyrimidine (Aldrich) (5.0 g, 25.64 mmol) in dry THF (130 mL) at −78° C. under nitrogen was slowly added a solution of 2.0 M LDA (23.0 mL, 1.8 eq) in THF via a syringe. The resulting mixture was stirred at −78° C. for an additional 20 minutes, after which 2-chlorobenzaldehyde (Aldrich) (7.2 mL, 2 eq) was added dropwise via a 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, and the mixture was allowed to warm to room temperature. The aqueous layer was separated and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and concentrated to give the crude product (14.2 g) as an oil. Purification using Flash Column Chromatography on Silica Gel, eluting with 5% ethyl acetate in hexanes gave the title compound (8.60 g, (M+H)+=336, M.P.=109.5-112.5° C.) which crystallized upon standing to give a white solid.

1. stirringThe reaction mixture was stirred for an additional 30 minutes at −78° C.
2. customquenched with saturated ammonium chloride solution
3. additionEthyl acetate was added
4. temperatureto warm to room temperature
5. customThe aqueous layer was separated
6. extractionextracted with ethyl acetate
7. washThe combined organic layers were washed with brine
8. dry with materialdried over magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated
11. customto give the crude product (14.2 g) as an oil
12. customPurification
13. washeluting with 5% ethyl acetate in hexanes

ORD record

ord-fa2eaff714e9456fac0cdbf96036ece3

Source dataset

uspto-grants-2009_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07566708B2