Ethyl isobutyrate → Ethyl tetrahydro-4-hydroxy-alpha,alpha-dimethyl-2H-pyran-4-acetate

Temperature

-50 °C

Step A To a hexane solution (Aldrich, 2 M) of LDA (78 mL, 160 mmol) in tetrahydrofuran (100 mL) at −50° C. was added a solution of isobutyric acid ethyl ester (Alfa) (17 mL, 127 mmol) in tetrahydrofuran (20 mL) dropwise. The reaction mixture was stirred −50° C. for 1 h, then a tetrahydrofuran solution (10 mL) of tetrahydro-pyran-4-one (Aldrich) (9.8 g, 98 mmol) was added dropwise. The reaction mixture was warmed up to room temperature and stirred for 18 h. Aqueous saturated NH4Cl was added to quench the reaction. The mixture was extracted with ethyl ether. The organic layer was separated, and the aqueous layer was extracted with ethyl ether. The organic layers were combined, washed with brine, water, dried over MgSO4, and concentrated to give 2-(4-hydroxy-tetrahydro-pyran-4-yl)-2-methyl-propionic acid ethyl ester as a yellow oil (19.5 g, 92%).

1. temperatureThe reaction mixture was warmed up to room temperature
2. stirringstirred for 18 h
3. customto quench
4. customthe reaction
5. extractionThe mixture was extracted with ethyl ether
6. customThe organic layer was separated
7. extractionthe aqueous layer was extracted with ethyl ether
8. washwashed with brine, water
9. dry with materialdried over MgSO4
10. concentrationconcentrated

ORD record

ord-72fe4ac9125b46508f194dc4576dc365

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08354444B2