Acetone → 4-Hydroxy-4-methyl-pent-2-ynoic acid ethyl ester

To a stirred solution of propynoic acid ethyl ester (20 mL, 197 mmol) in a mixture of 300 mL tetrahydrofuran:ether:pentane (4:1:1 by volume) cooled in a dry ice/isopropanol bath was added n-butyllithium (79 mL, 197 mmol, 2.5 M in hexanes) dropwise. After 15 minutes, anhydrous acetone (13.1 mL, 197 mmol) was slowly added. The reaction was kept below −78° C. for 8 h and quenched with an aqueous ammonium chloride solution, and the resulting mixture was stirred for 5 min. The reaction was warmed up to room temperature and extracted repeatedly with ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo, and the residue was purified via silica gel column chromatography (0-15% ethyl acetate in heptane) to give the title compound (10.75 g, 68.8 mmol) as a yellow oil.

1. temperaturecooled in a dry ice/isopropanol bath
2. waitThe reaction was kept below −78° C. for 8 h
3. customquenched with an aqueous ammonium chloride solution
4. extractionextracted repeatedly with ethyl acetate
5. dry with materialThe combined organic layers were dried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customthe residue was purified via silica gel column chromatography (0-15% ethyl acetate in heptane)

ORD record

ord-9442bc55044d486eaf472b18a95ebc53

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08349883B2