Lithium diisopropylamide → 1-(4-Trifluoromethyl-6-chloropyrimidin-5-yl)-1-(2-chloro-4-methoxypyrimidin-5-yl)methanol

4-Chloro-6-trifluoromethylpyrimidine (1.10 g, 6.02 mmol) in THF (15 ml) was added to a solution of lithium diisopropyl amide (LDA) (prepared from n-BuLi (3.7 ml, 5.9 mmol, 1.6M in hexanes) added to diisopropylamine (820 ul, 591 mg, 5.84 mmol) in THF (30 ml) at -78° C., allowing to warm to room temperature for 30 minutes, and re-cooling to -78° C.) at -78° C. The solution turned brown and was stirred for 10 minutes. Then 2-chloro-4-methoxypyrimidine-5-carboxaldehyde (0.96 g, 5.56 mmol) in THF (25 ml) was added dropwise and allowed to stir at -78° C. for 1 hour. The solution was quenched at -78° C. with 30% aqueous HOAc, diluted with water and extracted with EtOAc (3 times). The combined extracts were washed with brine (sat.), dried (MgSO4), filtered and concentrated in vacuo to give 1.61 g of crude product. Preparative radial chromatography (SiO2 ; hexane/EtOAc gradient elution) gave 190 mg (21% based on 530 mg of recovered starting material) of 1-(4-trifluoromethyl-6-chloropyrimidin-5-yl)-1-(2-chloro-4-methoxypyrimidin-5-yl)methanol.

1. stirringto stir at -78° C. for 1 hour
2. customThe solution was quenched at -78° C. with 30% aqueous HOAc
3. additiondiluted with water
4. extractionextracted with EtOAc (3 times)
5. washThe combined extracts were washed with brine (sat.)
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customto give 1.61 g of crude product
10. washPreparative radial chromatography (SiO2 ; hexane/EtOAc gradient elution)

ORDレコード

ord-7b40edb04a7148c28bea9004b250e968

出典データセット

uspto-grants-1998_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US05714438