Hydrochloric Acid → 2,2-Difluoro-3-hydroxypentanoic acid

Into a 10-L glass flask with a dropping funnel, 784 g (purity: 98%, 4.30 mol) of 2,2-difluoro-3-hydroxy-pentanoic acid ethyl ester, 300 mL of methanol and 2400 mL of water were added. The glass flask was cooled with ice water, followed by dropping 515 g (6.18 mol/1.4 eq) of 48% aqueous sodium hydroxide solution into the glass flask over 2 hours. The resulting solution was heated to room temperature and stirred for 1 hour. The completion of the reaction was confirmed by gas chromatography. The solution was washed twice with 800 mL of diisopropyl ether. The glass flask was again cooled with ice water. Then, 717 g (6.88 mmol/1.6 eq) of concentrated hydrochloric acid was dropped into the glass flask. After confirming that the pH of the solution was 1, the solution was stirred for 1 hour at room temperature. Subsequently, the solution was separated into an organic layer and an aqueous layer with the addition of 1000 mL of a mixed solution of diisopropyl ether and ethyl acetate. The aqueous layer was extracted three times with 1000 mL of a mixed solution of diisopropyl ether and ethyl acetate. The thus-obtained organic layers were combined and concentrated under a reduced pressure. With this, 683 g of 2,2-difluoro-3-hydroxy-pentanoic acid was obtained (yield: 98%, purity: 95%).

1. customover 2 hours
2. washThe solution was washed twice with 800 mL of diisopropyl ether
3. temperatureThe glass flask was again cooled with ice water
4. stirringthe solution was stirred for 1 hour at room temperature
5. customSubsequently, the solution was separated into an organic layer
6. additionan aqueous layer with the addition of 1000 mL of a mixed solution of diisopropyl ether and ethyl acetate
7. extractionThe aqueous layer was extracted three times with 1000 mL of a mixed solution of diisopropyl ether and ethyl acetate
8. concentrationconcentrated under a reduced pressure

ORD record

ord-2a8b227596ba4e8dbee3ae1ad386529e

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08592540B2