Acetaldehyde → (S)-3-[2-(1-Hydroxy-ethyl)-2-methyl-but-3-enoyl]-4-isopropyl-oxazolidin-2-one

A cooled (−78° C.) solution of (S)-4-isopropyl-3-((E)-2-methyl-but-2-enoyl)-oxazolidin-2-one (the enantiomer of the previously described compound 77a) (2.316 g, 10.962 mmol) in anhydrous dichloromethane (50 mL) was treated with a solution of titanium(IV) chloride (1 M, 12 mL, 11.510 mmol) in dichloromethane. After stirring the orange solution for 5 minutes, the mixture was treated with N,N-diisopropylethylamine (4.8 mL, 27.405 mmol). After stirring at −78° C. for 2 h, the purple solution was treated with acetaldehyde (4.3 mL, 76.374 mmol). After stirring at −78° C. for 1.5 h and at room temperature for 50 minutes, the reaction was quenched with a saturated solution of ammonium chloride (60 mL). The aqueous layer was extracted with dichloromethane. The organics were combined, filtered through a phase separator and the volatiles were removed in vacuo. The residue was purified by silica gel chromatography using a 100 g Isolute cartridge eluted with a continuous gradient of iso-hexanes/diethyl ether 1:0 to 1:1 to afford the title compound (1.742 g, 62%) as a 1:1.13:1.85:2.60 mixture of diastereoisomers and as a yellow oil.

1. stirringAfter stirring at −78° C. for 2 h
2. stirringAfter stirring at −78° C. for 1.5 h and at room temperature for 50 minutes
3. customthe reaction was quenched with a saturated solution of ammonium chloride (60 mL)
4. extractionThe aqueous layer was extracted with dichloromethane
5. filtrationfiltered through a phase separator
6. customthe volatiles were removed in vacuo
7. customThe residue was purified by silica gel chromatography
8. washeluted with a continuous gradient of iso-hexanes/diethyl ether 1:0 to 1:1

ORD record

ord-c8408ded123c4eaeb87a095927e6fb17

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09145441B2