Water → 1-(3-Hydroxy-2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-yl)-4-(4-methoxyphenyl)piperazine

Temperature

0 °C

n-Butyllithium (hexane solution 1.50 M, 3.40 mL, 5.10 mmol) was added dropwise to solution of 4-bromotoluene (1.10 g, 6.43 mmol) in THF (10 ml) under a stream of argon at −70° C. or less and the mixture was stirred for 30 minutes. To the mixture was added dropwise a solution of 4-(4-methoxyphenyl)-1-(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-3-on-5-yl)piperazine (1.00 g, 2.5 mmol) obtained in Reference Example 13 in THF (3 ml) at −70° C. or less and the mixture was allowed to warm to 0° C. After stirring under ice cooling for 30 minutes, the resulting mixture was poured into water and extracted with ethyl acetate. The organic extract was washed with water and saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified with silica gel column chromatography (hexane/ethyl acetate=5/1) to obtain 1.11 g (yield 90%) of the title compound via recrystallization (ethyl acetate-hexane). mp. 145–147° C.

1. stirringAfter stirring under ice cooling for 30 minutes
2. extractionextracted with ethyl acetate
3. extractionThe organic extract
4. washwas washed with water and saturated aqueous sodium chloride
5. dry with materialdried over anhydrous sodium sulfate
6. concentrationconcentrated under reduced pressure
7. customThe residue was purified with silica gel column chromatography (hexane/ethyl acetate=5/1)

ORD record

ord-4856cdaac2a749318d961888c14361f6

Source dataset

uspto-grants-2007_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07208495B2