Sodium hydride → tert-butyl (2S,5S)-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-[(2-fluoro-6-nitrophenoxy)methyl]morpholine-4-carboxylate

온도

0 °C

To a stirring solution of sodium hydride (0.257 g, 6.43 mmol) (pre-washed in hexanes) in DMF (15.30 mL) at 0° C., tert-butyl (2S,5S)-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-(hydroxymethyl)morpholine-4-carboxylate (Example 1, Step 5) (1.66 g, 4.59 mmol) in DMF (2 mL) was added dropwise. The resulting mixture was stirred at 0° C. for 1 hour. At this point, 1,2-difluoro-3-nitrobenzene (0.494 mL, 4.50 mmol) in 0.5 mL of DMF was added dropwise and the final solution was slowly warmed toward room temperature and stirred for 1 hour. Complete by LC/MS at this time. The contents were quenched by adding saturated aqueous sodium bicarbonate and then extracted between water and EtOAc (3×75 mL). The organic layer was dried over MgSO4, filtered and concentrated. Purification on silica gel (120 g) eluting with a gradient of 0-60% EtOAc/hexanes afforded the title compound (1.68 g, 3.36 mmol, 73% yield) as a yellow oil, MS (ESI): m/z=401.11 (M+H-boc).

1. stirringstirred for 1 hour
2. customThe contents were quenched
3. additionby adding saturated aqueous sodium bicarbonate
4. extractionextracted between water and EtOAc (3×75 mL)
5. dry with materialThe organic layer was dried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated
8. customPurification on silica gel (120 g)
9. washeluting with a gradient of 0-60% EtOAc/hexanes

ORD 기록

ord-e9ed9e102eec44a1b72b5c684282f7a3

출처 데이터셋

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09315475B2