Hydrochloric Acid → Benzoic acid, 4-(3-hydroxypropyl)-

Temperature

-78 °C

1.7M n-butyllithium in hexane (19.4 ml, 33 mmole) was added dropwise to a chilled (-78° C.) and stirred solution of diisopropylamine (4.63 ml, 33 mmole) in 20 ml of dry tetrahydrofuran (hereinafter THF). After 20 minutes, a solution of p-toluic acid (2.042 g, 15 mmole) in 20 ml of dry THF was added dropwise. After stirring at -78° C. for another 1.5 hours, 4 ml of HMPA was added followed immediately by a solution of ethylene oxide (2.99 g, 67.9 mmole) in 10 ml of dry THF. The resulting solution was stirred at -78° C. for 2 hours, treated with 5% hydrochloric acid and warmed up to room temperature, the THF being removed in vacuo. The aqueous solution was saturated with sodium chloride and extracted three times with ethyl ether. The combined ether extracts were concentrated from 300 to 100 ml and extracted with a 0.5N sodium hydroxide solution. This extract was acidified with 10% hydrochloric acid and extracted three times with ethyl ether. The ether extracts were dried over anhydrous magnesium sulfate and evaporated to a residue. This residue was chromatographed on a silica gel column, eluting successively with dichloromethane-ethyl acetate (9:1 and 1:1), ethyl acetate and dichloromethane-methanol (9:1) to give 750 mg of the title A compound, with consistent spectral data.

1. stirringThe resulting solution was stirred at -78° C. for 2 hours
2. temperaturewarmed up to room temperature
3. customthe THF being removed in vacuo
4. extractionextracted three times with ethyl ether
5. concentrationThe combined ether extracts were concentrated from 300 to 100 ml
6. extractionextracted with a 0.5N sodium hydroxide solution
7. extractionextracted three times with ethyl ether
8. dry with materialThe ether extracts were dried over anhydrous magnesium sulfate
9. customevaporated to a residue
10. customThis residue was chromatographed on a silica gel column
11. washeluting successively with dichloromethane-ethyl acetate (9:1 and 1:1), ethyl acetate and dichloromethane-methanol (9:1)
12. customto give 750 mg of the title A compound

ORD record

ord-384e6b71b772406485e297e6fe10bb17

Source dataset

uspto-grants-1990_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04906667