Toluene → (S)-4-(2-Hydroxy-2-methylpropyl)oxazolidin-2-one

Methylmagnesium bromide (227 mL of 3M solution in diethyl ether) was added to a mixture of toluene (340 mL) and THF (340 mL) at −20° C. A warm THF solution (170 mL) of the ester from Step 2 (40 g) was then added dropwise maintaining the temperature below −10° C. The mixture was aged for 2 hours and was then slowly added to a mixture of water (1000 mL) and acetic acid (200 mL) and the resultant mixture was stirred for 2 hours at room temperature. The aqueous layer was separated and the organic layer was extracted with water (2×200 mL). The product was extracted from the combined aqueous layers using dichloromethane and a continuous extractor. The dichloromethane extract was evaporated to dryness using heptane as a co-solvent to azeotrope off the acetic acid. The residue was purified by chromatography on SiO2 using ethanol and dichloromethane (1:30) to yield (4S)-4-(2-hydroxy-2-methylpropyl)-1,3-oxazolidin-2-one.

1. temperaturemaintaining the temperature below −10° C
2. customThe aqueous layer was separated
3. extractionthe organic layer was extracted with water (2×200 mL)
4. extractionThe product was extracted from the combined aqueous layers
5. extractionThe dichloromethane extract
6. customwas evaporated to dryness
7. customThe residue was purified by chromatography on SiO2

ORD record

ord-6afc2467327e46e89a26fc6574eee2bf

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08318748B2