Tetrahydrofuran → HCID 117974480, compound

Temperature

-78 °C

To a solution of (R)-4-benzyloxazolidin-2-one (7.5 g, 42.3 mmol) in anhydrous THF (140 mL) was added n-BuLi (17.8 mL of 2.5 M in hexanes, 44.4 mmol) dropwise at −78° C. over a 20 min period. The solution was clear to light yellow during most of the addition and then gradually turns orange upon completion. The resulting orange solution was stirred at −78° C. for 45 min and was then treated dropwise with the propanoyl chloride prepared above at −75 to −78° C. The resulting light brown solution was stirred at −78° C. for 2 h, slowly warmed to room temperature, and stirred for 16 h at room temperature. The homogeneous brown solution was neutralized with saturated aqueous ammonium chloride (NH4Cl, 100 mL), and the majority of the THF was removed on the rotary evaporator. The aqueous residue was extracted with CH2Cl2 (3×100 mL), and the combined organic extracts were washed with brine (100 mL), dried over sodium sulfate (Na2SO4), filtered, and concentrated to a tan solid. The solid was recrystallized from 25% ethyl acetate (EtOAc) in hexanes (150 mL), and the resulting crystals were collected by vacuum filtration, washed with ice cold 20% EtOAc in hexanes, and dried under vacuum to give (R)-4-benzyl-3-(3-(p-tolyl)propanoyl)oxazolidin-2-one (10.57 g, 77%) as pale yellow needles: mp 124-126° C.; 1H NMR (400 MHz, CDCl3) δ 7.29 (m, 3H), 7.17 (m, 4H), 7.11 (m, 2H), 4.65 (m, 1H), 4.16 (m, 2H), 3.26 (m, 3H), 2.99 (m, 2H), 2.75 (m, 1H), 2.32 (s, 3H); ESIMS m/z 346 ([M+Na]+).

1. additionmost of the addition
2. customprepared above at −75 to −78° C
3. stirringThe resulting light brown solution was stirred at −78° C. for 2 h
4. temperatureslowly warmed to room temperature
5. stirringstirred for 16 h at room temperature
6. customthe majority of the THF was removed on the rotary evaporator
7. extractionThe aqueous residue was extracted with CH2Cl2 (3×100 mL)
8. washthe combined organic extracts were washed with brine (100 mL)
9. dry with materialdried over sodium sulfate (Na2SO4)
10. filtrationfiltered
11. concentrationconcentrated to a tan solid
12. customThe solid was recrystallized from 25% ethyl acetate (EtOAc) in hexanes (150 mL)
13. filtrationthe resulting crystals were collected by vacuum filtration
14. washwashed with ice cold 20% EtOAc in hexanes
15. customdried under vacuum

ORD record

ord-87980a86855c4d0883e22f0cb5aa944d

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09179674B2