Hexane → 5-[Hydroxy-(tetrahydro-pyran-4-yl)-methyl]-3-methoxy-2-(2,4,6-trimethyl-phenyl)-cyclopent-2-enone

Temperature

-78 °C

To a solution of N-ethyl-N,N-diisopropylamine (527 μl, 3.76 mmol) in THF (5 ml) under N2 at −78° C. is added, dropwise, a 2.5M solution of butyllithium in hexane (1.32 ml, 3.3 mmol) and the reaction allowed to stir at −78° C. for 20 minutes. This pale yellow solution is then added dropwise, over a period of 10 minutes, to a solution of 2-(2,4,6-trimethylphenyl)-3-methoxy-cyclopent-2-enone (691 ml, 3 mmol) in THF (5 ml) under N2, which is pre-cooled to −78° C. The resulting solution is allowed to stir at −78° C. for 40 minutes. A solution of tetrahydropyran-4-carbaldehyde (377 mg, 3.3 mmol) in THF (1 ml) is then added in one portion, the reaction mixture is stirred at −78° C. for 30 minutes before being allowed to warm to room temperature over a period of 60 minutes. The reaction was quenched by the addition of saturated aqueous ammonium chloride (50 ml) and extracted with ethyl acetate (2×50 ml). The combined organics were purified by flash chromatography to give 5-[hydroxy-(tetrahydro-pyran-4-yl)-methyl]-3-methoxy-2-(2,4,6-trimethyl-phenyl)-cyclopent-2-enone (648 mg).

1. temperaturewhich is pre-cooled to −78° C
2. stirringto stir at −78° C. for 40 minutes
3. stirringthe reaction mixture is stirred at −78° C. for 30 minutes
4. temperatureto warm to room temperature over a period of 60 minutes
5. customThe reaction was quenched by the addition of saturated aqueous ammonium chloride (50 ml)
6. extractionextracted with ethyl acetate (2×50 ml)
7. customThe combined organics were purified by flash chromatography

ORD record

ord-51cb9185e5c4454bac7cd027d2239b2c

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09096560B2