Ethyl Acetate → HCID 90422856, compound

Temperature

0 °C

To a solution of benzyl((2R,3R)-3-(tert-butoxy)-1-hydroxybutan-2-yl)carbamate (5.88 g, 19.9 mmol) in 100 mL DMF was added NaH (60% in mineral oil, 1.62 g, 40.6 mmol) at 0° C. The reaction mixture was stirred for 30 min at 0° C. To the reaction mixture were added 4-methoxybenzyl chloride (4.07 mL, 29.9 mmol) and tetrabutylammonium iodide (0.74 g, 1.99 mmol) and the resulting mixture was warmed to room temperature and stirred for 15.5 h. The reaction mixture was poured into ice water (200 mL) forming a white suspension. EtOAc (100 mL) was added and the resulting mixture was stirred for 5 min to form a clear two layer solution. After separation, the aqueous phase was extracted with EtOAc (100 mL×3). The combined organic solution was washed with brine (80 mL), dried over Na2SO4, filtered and concentrated. Flash column chromatography (EtOAc/Heptane 0 to 70%) gave 5.90 g of (R)-4-((R)-1-(tert-butoxy)ethyl)-3-(4-methoxybenzyl)oxazolidin-2-one with minor impurities. Major product 1H NMR (400 MHz, MeOD) δ 7.38-7.29 (m, 2H), 6.99-6.93 (m, 2H), 4.68-4.58 (m, 1H), 4.33 (dd, J=9.3, 4.5 Hz, 1H), 4.27-4.17 (m, 2H), 3.89 (dd, J=6.4, 4.8 Hz, 1H), 3.81 (s, 3H), 3.65 (dd, J=9.0, 4.6 Hz, 1H), 1.09 (s, 9H), 1.02 (d, J=6.3 Hz, 3H). MS m/z 308.2 (M+H).

1. temperaturethe resulting mixture was warmed to room temperature
2. stirringstirred for 15.5 h
3. customforming a white suspension
4. stirringthe resulting mixture was stirred for 5 min
5. customto form a clear two layer solution
6. customAfter separation
7. extractionthe aqueous phase was extracted with EtOAc (100 mL×3)
8. washThe combined organic solution was washed with brine (80 mL)
9. dry with materialdried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated

ORD record

ord-eeb454d1dc75494693aa19eccfa8f2f4

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09434719B2