2,5-Dibromopyridine → (2R)-1-(5-bromopyridin-2-yl)-2-((tetrahydro-2H-pyran-2-yl)oxy)propan-1-one

2,5-dibromopyridine (5 g, 21.1 mmol) was dissolved in dried toluene (100 mL), cooled to −78° C., to which n-butyl lithium (9 mL, 22.5 mmol, 2.5 M solution in n-hexane) was added dropwise. The mixture was allowed to react at −78° C. for 2 hrs, and then the solution of (2R)-1-morpholino-2-((tetrahydro-2H-pyran-2-yl)oxy)propan-1-one (7.7 g, 31.6 mmol) in toluene was added dropwise and allowed to react at −78° C. for 5 hrs. The reaction was monitored by TLC (petroleum ether). After the reaction completed, the reaction was quenched by adding saturated solution of ammonium chloride. The mixture was raised to room temperature and diluted with water. The toluene layer was separated and extracted with ethyl acetate. The organic phase was combined, washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, and then dried by rotary dryer. Column chromatography (petroleum ether) afforded 4.1 g of pale yellow solid (compound 1a), yield 62%.

1. additionwas added dropwise
2. customto react at −78° C. for 2 hrs
3. customto react at −78° C. for 5 hrs
4. customthe reaction was quenched
5. additionby adding saturated solution of ammonium chloride
6. additiondiluted with water
7. customThe toluene layer was separated
8. extractionextracted with ethyl acetate
9. washwashed with saturated sodium chloride solution
10. dry with materialdried over anhydrous sodium sulfate
11. customdried by rotary dryer

ORD 기록

ord-b07c862e80b841e3a0aaff45bbbefa03

출처 데이터셋

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09416144B2