Acetone → 4-(2-Hydroxypropan-2-yl)benzoic acid

Temperature

-40 °C

To a solution of 4-iodobenzoic acid (2.5 g, 10 mmol) in tetrahydrofuran (20 mL) was added lithium chloride (0.42 g, 10 mmol). Then isopropylmagnesium chloride (5 mL, 2 mol/L in tetrahydrofuran) was injected in at −40° C. under nitrogen atmosphere. The reaction mixture was stirred at −40° C. for 1 hour. Then isopropylmagnesium chloride (6 mL, 2 mol/L in tetrahydrofuran) was injected and the reaction was stirred at −40° C. for additional 1 hour. To the solution was added acetone (0.58 g, 10 mmol), and the mixture was stirred at −40° C. for 0.5 hour, then stirred at room temperature for 0.5 hour. After the reaction, the mixture was poured into water (50 mL), hydrochloric acid (3 mol/L) was added to make pH 3-4. and the product was extracted with dichloromethane (50 mL), dried over anhydrous sodium sulfate, concentrated and purified by column chromatography (silica gel dichloromethane:methanol=15:1) to give the pure product 4-(2-hydroxypropan-2-yl)benzoic acid (1.5 g, 83%) as a white solid. 1H NMR (CDCl3, 300 MHz) δ: 8.08 (d, J=8.7 Hz, 2H), 7.60 (d, J=8.4 Hz, 2H), 1.61 (s, 6H).

1. customwas injected in at −40° C. under nitrogen atmosphere
2. stirringthe reaction was stirred at −40° C. for additional 1 hour
3. stirringthe mixture was stirred at −40° C. for 0.5 hour
4. stirringstirred at room temperature for 0.5 hour
5. customAfter the reaction
6. additionwas added
7. extractionand the product was extracted with dichloromethane (50 mL)
8. dry with materialdried over anhydrous sodium sulfate
9. concentrationconcentrated
10. custompurified by column chromatography (silica gel dichloromethane:methanol=15:1)

ORD record

ord-10609d57cac24ad18d1234b2e8ef11b3

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09409865B2