Tetrahydrofuran → 4-(Prop-2-en-1-yloxy)benzoic acid

Temperature

50 °C

To a mixture of methyl 4-allyloxybenzoate (10.0 g), THF (50 mL) and methanol (50 mL) was added 2N aqueous NaOH solution (50 mL), and the mixture was stirred at 50° C. for 40 minutes. The reaction solution was concentrated to about 50 g, washed with hexane, and acidified with conc. hydrochloric acid. The precipitated crystals were collected by filtration, dissolved in ethyl acetate, dried over magnesium sulfate, and the solvent was evaproated under reduced prssure to give crude crystals of 4-allyloxybenzoic acid (4.68 g, 50%). To the crystals were added dichloroethane (50 mL) and DMF (2 drops), and the mixture was heated to 80° C., and thereto was added dropwise thionyl chloride (4.61 g) over a period of 10 minutes. The mixture was stirred for 30 minutes, and the reaction solution was concentrated to give an oily acid chloride (5.3 g). The compound (3.81 g) of Example 6-1 and the above acid chloride (5.07 g) were dissolved in methylene chloride (50 mL), and thereto was added boron trifluoride diethyl ether complex (4.39 g), and the mixture was allowed to stand at room temperature for 5 days. The reaction solution was washed successively with aqueous hydrochloric acid, water, and aqueous sodium hydroxide solution, dried, filtered, and concentrated. The residue was purified by silica gel chromatography to give a mixture of (1-p-toluenesulfonyl-1H-pyrrol-2-yl) (4-allyloxyphenyl) ketone and 4-allyloxybenzoic acid. This mixture was dissolved in 1N aqueous NaOH solution, and extracted three time with ethyl acetate. The combined oil layer was dried and concentrated to give crude crystals of (1-p-toluenesulfonyl-1H-pyrrol-2-yl) (4-allyloxyphenyl) ketone (5.79 g), which was dissolved in methanol (70 mL), and thereto was added 5N aqueous NaOH solution (70 mL), and the mixture was heated for 1.5 hour. The methanol was evaporated under reduced pressure, and extracted with ethyl acetate, dried, and concentrated. The residue was purified by silica gel column chromatography to give (1H-pyrrol-2-yl) (4-allyloxyphenyl) ketone (2.51 g, 43%).

1. concentrationThe reaction solution was concentrated to about 50 g
2. washwashed with hexane
3. filtrationThe precipitated crystals were collected by filtration
4. dissolutiondissolved in ethyl acetate
5. dry with materialdried over magnesium sulfate

ORD record

ord-8c75438e2f7f45599d8f6ee3638a927c

Source dataset

uspto-grants-2004_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06759429B2