Lithium diisopropylamide → HCID 67775028, compound

A solution of 2-[2-(4-Chloro-phenyl)-5-methyl-pyrimidin-4-yl]-3-methoxy-cyclopent-2-enone (69.5 mg, 0.22 mmol) in anhydrous tetrahydrofuran (3 ml), under nitrogen, was cooled to −78° C. and stirred for 10 minutes before the drop wise addition of lithium diisopropylamide (as a 2.0M solution in hexane/tetrahydrofuran/ethylbenzene) (0.14 ml, 0.28 mmol). The resulting brown solution was stirred at −78° C. for a further 45 minutes before the drop wise addition of 4-formyltetrahydropyran (34 mg, 0.30 mmol). The orange solution was then warmed to room temperature. After 2.5 h the reaction was shown to have reached a steady state and was therefore quenched with saturated ammonium chloride (5 ml), ethyl acetate (5 ml) and water (1 ml). The biphasic mixture was separated and the aqueous layer further extracted with ethyl acetate (2×5 ml). Combined organics were dried over magnesium sulphate, filtered and stripped to dryness to yield a yellow oil. This was purified by normal phase chromatography (100% dichloromethane−5% methanol:dichloromethane) to give 2-[2(4-Chloro-phenyl)-5-methyl-pyrimidin-4-yl]-5-[hydroxy-(tetrahydro-pyran-4-yl)-methyl]-3-methoxy-cyclopent-2-enone as a dark yellow oil (50.3 mg, 0.12 mmol, 53% yield).

1. customwas therefore quenched with saturated ammonium chloride (5 ml), ethyl acetate (5 ml) and water (1 ml)
2. customThe biphasic mixture was separated
3. extractionthe aqueous layer further extracted with ethyl acetate (2×5 ml)
4. dry with materialCombined organics were dried over magnesium sulphate
5. filtrationfiltered
6. customto yield a yellow oil
7. customThis was purified by normal phase chromatography (100% dichloromethane−5% methanol:dichloromethane)

ORD record

ord-98f9d2b739f44bffa4364ece871e48ad

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09051300B2