(3R,4S,5R,6R)-3,4,5-Tris-trimethylsilanyloxy-6-trimethylsilanyloxymethyl-tetrahydro-pyran-2-on → (2S,3R,4R,5S,6R)-2-(4-chloro-5-(4-ethylbenzyl)-2-(2-(2,2,2-trifluoroethoxy)ethoxy)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol

Temperature

-78 °C

To a solution of 1-bromo-4-chloro-5-(4-ethylbenzyl)-2-(2-(2,2,2-trifluoroethoxy)ethoxy)benzene (BR) (96 mg, 0.21 mmol) and (3R,4S,5R,6R)-3,4,5-tris(trimethylsilyloxy)-6-((trimethylsilyloxy)methyl)-tetrahydropyran-2-one (0.20 g, 0.43 mmol) in anhydrous THF (3 mL), was added n-BuLi (1.6 M, 0.40 mL) in a dropwise fashion at −78° C. over 15 min. The resulting solution was stirred at −78° C. for 30 min. After quenching with methanesulfonic acid (61 μL in 1.0 mL MeOH), the mixture was allowed to warm to room temperature and stirred overnight. The reaction mixture was filtered through silica and purified by preparative TLC eluting with 7% MeOH in CH2Cl2 to collect the crude product. To a solution of the crude product in a mixture of 1:1 CH3CN:CH2Cl2 (4 mL) was added Et3SiH (200 μL), followed by cooling to −40° C. To the cooled mixture was added BF3.Et2O (40 μL), and it was allowed to warm to 0° C. over 2 h. Triethylamine (100 μL) was then added, the mixture was evaporated, and the residue was purified by preparative HPLC to give compound BS. 1H-NMR (CD3OD, 300 MHz) δ 7.32 (s, 1H), 7.04 (m, 5H), 4.59 (d, J=9.3 Hz, 1H), 416-3.96 (m, 8H), 3.66-3.30 (m, 7H), 2.57 (q, J=7.5, 2H), 1.19 (t, J=7.2 Hz, 3H); MS ESI m/z 532.8 (M−1).

1. customAfter quenching with methanesulfonic acid (61 μL in 1.0 mL MeOH)
2. temperatureto warm to room temperature
3. stirringstirred overnight
4. filtrationThe reaction mixture was filtered through silica
5. custompurified by preparative TLC
6. washeluting with 7% MeOH in CH2Cl2
7. customto collect the crude product
8. additionTo a solution of the crude product in a mixture of 1:1 CH3CN
9. additionCH2Cl2 (4 mL) was added Et3SiH (200 μL)
10. temperatureby cooling to −40° C
11. additionTo the cooled mixture was added BF3.Et2O (40 μL), and it
12. temperatureto warm to 0° C. over 2 h
13. additionTriethylamine (100 μL) was then added
14. customthe mixture was evaporated
15. customthe residue was purified by preparative HPLC
16. customto give compound BS

ORD record

ord-5b8ea2c35a4c4b58a0ec8c3b9a628c28

Source dataset

uspto-grants-2010_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07838498B2