Triethylamine → (S)-3-[3-[4-(1,1-dimethylethyl)phenyl]-1-oxopropyl]-4-(phenylmethyl)-2-oxazolidinone

Temperature

0 °C

To a stirring solution at -78° C. of 4-(1,1-dimethylethyl)benzenepropanoic acid (1.29 g, 6.25 mmol) and triethylamine (1.05 mL, 7.51 mmol) in dry THF (26 mL) was added pivaloylchloride (0.77 mL, 6.25 mmol) dropwise. After the addition, the mixture was stirred at -78° C. for 10 minutes and at 0° C. for 30 minutes. During this time metalated oxozolidinone was prepared separately by dropwise addition of n-butyl lithium (4.29 mL of a 1.6M solution in hexane) to a solution of (S)-(-)-4-benzyl-2-oxazolidinone (1.23 g of 99% pure, 6.88 mmol) in dry THF (26 mL). The metalated oxazolidinone solution was then added, at -78° C., via a cannula to the previously prepared reaction mixture and stirred for 1 h at 0° C. The reaction was quenched at 0° C. by addition of saturated NH4Cl solution (16 mL) and was concentrated. Saturated NH4Cl solution (25 mL) was added to the residue and the mixture was extracted with CH2Cl2 (3×100 mL). The combined organic phases were washed with saturated NaHCO3 (100 mL) and dried (NaSO4). Filtration and concentration provided crude product (2.50 g) which was purified via flash chromatography, eluting with a mixture of EtOAc and hexane (1:3) to provide (S)-3-[3-[4-(1,1-dimethylethyl)phenyl]-1-oxopropyl]-4-(phenylmethyl)-2-oxazolidinone (1.82 g, 4.98 mmol) in 80% yield, mp 123°-126° C.

1. additionAfter the addition
2. stirringstirred for 1 h at 0° C
3. customThe reaction was quenched at 0° C. by addition of saturated NH4Cl solution (16 mL)
4. concentrationwas concentrated
5. additionSaturated NH4Cl solution (25 mL) was added to the residue
6. extractionthe mixture was extracted with CH2Cl2 (3×100 mL)
7. washThe combined organic phases were washed with saturated NaHCO3 (100 mL)
8. dry with materialdried (NaSO4)
9. filtrationFiltration and concentration
10. customprovided crude product (2.50 g) which
11. customwas purified via flash chromatography
12. washeluting with a mixture of EtOAc and hexane (1:3)

ORD record

ord-1f1fb29444ac48ba8db58c71e5988cee

Source dataset

uspto-grants-1992_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05128448