2-Thiophenecarboxaldehyde → [4-Chloro-2-(2-chloro-phenoxy)-pyrimidin-5-yl]-thiophen-2-yl-methanol

Temperature

-78 °C

4-Chloro-2-(2-chloro-phenoxy)-pyrimidine (432 mg, 1.79 mmol) was dissolved in 10 mL of dry THF, and the reaction mixture was cooled to −78° C. under nitrogen. Lithium diisopropylamine (1.6 mL of 2M solution in THF) was added and the reaction mixture was stirred for eight minutes. Thiophene-2-carboxaldehyde (0.31 mL) was added, and the reaction mixture was stirred for 30 minutes at −78° C. The reaction was quenched by addition of 10 mL saturated aqueous ammonium chloride, and evaporated under reduced pressure to remove THF. Water (40 mL) and EtOAc (60 mL) were added, the organic phase was collected, and the aqueous phase was washed twice with 40 mL EtOAc. The combined organic layers were washed with brine, dried over MgSO4, filtered, and evaporated under reduced pressure. The residue was purified by preparative TLC using 1.8% MeOH in methylene chloride to yield 98 mg of [4-Chloro-2-(2-chloro-phenoxy)-pyrimidin-5-yl]-thiophen-2-yl-methanol. Mass Spec. M+H=354.

1. stirringthe reaction mixture was stirred for 30 minutes at −78° C
2. customThe reaction was quenched by addition of 10 mL saturated aqueous ammonium chloride
3. customevaporated under reduced pressure
4. customto remove THF
5. additionWater (40 mL) and EtOAc (60 mL) were added
6. customthe organic phase was collected
7. washthe aqueous phase was washed twice with 40 mL EtOAc
8. washThe combined organic layers were washed with brine
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. customevaporated under reduced pressure
12. customThe residue was purified by preparative TLC

ORD record

ord-9edbf5f0b2a6440090c1806fe95028dc

Source dataset

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07452880B2