Tetrahydrofuran → 4-[1-(3-Cyclopentyloxy-4-methoxy-phenyl)ethyl]-5-methylpyrazol-3-one

Temperature

-78 °C

To a stirred solution of diethyl(N-methoxy-N-methyl-carbamoylmethyl)phosphonate (2.60 g, 10.90 mmol) in dry tetrahydrofuran (50 ml) at −78° C. was added lithium diisopropylamide (1.5M solution in cyclohexane, 7.33 ml, 11 mmol) dropwise over 3 minutes. The resulting solution was stirred at −78° C. for 30 minutes, after which time 3-cyclopentyloxy-4-methoxybenzaldehyde (1.5 g, 6.81 mmol) in dry tetrahydrofuran (5 ml) was added in one portion. The reaction was allowed to warm to room temperature and stirring continued overnight. After which time the reaction mixture was diluted with water (25 ml) and the tetrahydrofuran removed in vacuo. The aqueous residue was diluted with brine (25 ml) and extracted with methylene chloride (3×60 ml). The organic extracts were dried (Na2SO4) and evaporated in vacuo to give a yellow liquid. The liquid was purified by flash chromatography (SiO2; hexane/ethyl acetate (65:35)) to afford the title compound as a pale yellow liquid (1.986 g).

1. temperatureto warm to room temperature
2. stirringstirring continued overnight
3. customthe tetrahydrofuran removed in vacuo
4. additionThe aqueous residue was diluted with brine (25 ml)
5. extractionextracted with methylene chloride (3×60 ml)
6. dry with materialThe organic extracts were dried (Na2SO4)
7. customevaporated in vacuo
8. customto give a yellow liquid
9. customThe liquid was purified by flash chromatography (SiO2; hexane/ethyl acetate (65:35))

ORD record

ord-6567b1f9e65a4a7f95522b4d10c28bec

Source dataset

uspto-grants-2001_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06248769B1