Tetrahydrofuran → (5R)-3-(4-benzyloxy-3-fluoro-phenyl)-5-hydroxy-methyl-oxazolidin-2-one

온도

-78 °C

A stirred solution of 17.5 g (4-benzyloxy-3-fluoro-phenyl)-carbamic acid benzyl ester (MW: 351.38, 50 mmol) in 30 ml of dry tetrahydrofuran was cooled to −78° C. with a dry ice/acetone bath. 22.8 ml of a 2.3M n-butyl-lithium solution in n-hexane (52.5 mmol) was added drop wise and the reaction mixture stirred at −78° C. for 15 min. 7.92 g R(−)-glycidyl butyrate (MW: 144.17, 60 mmol) were added and the reaction was allowed to warm up to room temperature. The reaction was monitored by HPLC, quenched with a saturated ammonium chloride solution and diluted with 100 ml of ethyl acetate. The organic layer was washed with 200 ml water and 200 ml brine. The organic layer was dried over magnesium sulfate, filtered and the filtrate evaporated under reduced pressure. The residue was crystallized from 200 ml of a 1/1-ethyl acetate/hexane mixture. The solid was collected and recrystallized from 150 ml of a 9/1 ethyl acetate/dichloromethane mixture. The colorless crystals were collected and dried. Yield: 10.4-g, 65.5%. MS: 318.1 (M+H)+. Method ESI+.

1. temperatureto warm up to room temperature
2. customquenched with a saturated ammonium chloride solution
3. additiondiluted with 100 ml of ethyl acetate
4. washThe organic layer was washed with 200 ml water and 200 ml brine
5. dry with materialThe organic layer was dried over magnesium sulfate
6. filtrationfiltered
7. customthe filtrate evaporated under reduced pressure
8. customThe residue was crystallized from 200 ml of a 1/1-ethyl acetate/hexane mixture
9. customThe solid was collected
10. customrecrystallized from 150 ml of a 9/1 ethyl acetate/dichloromethane mixture
11. customThe colorless crystals were collected
12. customdried

ORD 기록

ord-81a593bb248943f09576c0f1356aeb6e

출처 데이터셋

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08158797B2