Acetic Acid → HCID 91211014, compound

TBAF (1.0 M in THF, 1.4 mL) and glacial acetic acid (80 μL, 5.9 mmol) were added dropwise to a solution of tert-butyldimethylsilyl 3,6-di-O-acetyl-2-azido-4-O-tert-butyldimethylsilyl-2-deoxy-β-D-glucopyranoside (590 mg, 1.14 mmol) in THF (12 mL) under nitrogen at 0° C. The reaction mixture was warmed to room temperature, stirred for 1.5 h and quenched with saturated NaHCO3 solution. After extraction with CH2Cl2 (3×), the combined organic phases were dried over MgSO4, filtered and the solvents were removed in vacuo. The crude material was dried by coevaporation with anhydrous toluene and vacuum for 1 h and dissolved in CH2Cl2 (25 mL). Trichloroacetonitrile (1.3 mL, 12.50 mmol) and freshly activated 4 Å powdered molecular sieves (300 mg) were added and the mixture was stirred for 30 minutes at room temperature. After cooling to 0° C., DBU (30 μl, 0.2 mmol) was added and the temperature was allowed to rise to room temperature. After 1 h, the mixture was filtered through Celite and the solvents were removed in vacuo. Flash chromatography on silica gel (Hexanes:EtOAc 85:15) afforded 13α (437 mg, 0.80 mmol, 70%) and 13β (94 mg, 0.17 mmol, 15%). 13α: 1H-NMR (500 MHz, CDCl3) δ 8.81 (s, 1H, NH), 6.44 (d, J=3.6 Hz, 1H, H-1), 5.43 (dd, J=8.8, 10.4 Hz, 1H, H-3), 4.41 (dd, J=1.9, 12.0 Hz, 1H, H-6a), 4.12-3.99 (m, 2H, H-6b, H-5), 3.87 (t, J=9.1 Hz, 1H, H-4), 3.58 (dd, J=3.6, 10.7 Hz, 1H, H-2), 2.17 (s, 3H, OCH3), 2.01 (s, 3H, OCH3), 0.86 (s, 9H, C(CH3)3), 0.08 (s, 3H, SiCH3), 0.06 (s, 3H, SiCH3); 13C-NMR (125 MHz, CDCl3) δ 170.5, 169.7, 160.8, 94.7, 72.77, 69.1, 62.5, 61.5, 25.9, 21.6, 21.0, 18.2, −3.8, −4.6. 13β: 1H-NMR (500 MHz, CDCl3) δ 8.81 (s, 1H, NH), 5.73 (d, J=8.2 Hz, 1H, H-1), 5.03 (dd, J=8.8 Hz, J=9.8 Hz, 1H, H-3), 4.40 (dd, J=2.1 Hz, J=11.9 Hz, 1H, H-6a), 4.13 (dd, J=4.2 Hz, J=11.9 Hz, 1H, H-6b), 3.87 (t, J=9.5 Hz, 1H, H-4), 3.58 (m, 2H, H-2, H-5), 2.17 (s, 3H, OCH3), 2.08 (s, 3H, OCH3),0.84 (s, 9H, C(CH3)3), 0.05 (s, 3H, SiCH3), 0.04 (s, 3H, SiCH3); 13C-NMR (125 MHz, CDCl3) δ 170.7, 169.9, 160.8, 96.6, 75.3, 68.8, 64.1, 62.4, 25.9, 25.8, 25.8, 21.5, 21.1, 18.1, −3.9, −4.8.

1. customquenched with saturated NaHCO3 solution
2. extractionAfter extraction with CH2Cl2 (3×)
3. dry with materialthe combined organic phases were dried over MgSO4
4. filtrationfiltered
5. customthe solvents were removed in vacuo
6. dry with materialThe crude material was dried by coevaporation with anhydrous toluene and vacuum for 1 h
7. dissolutiondissolved in CH2Cl2 (25 mL)
8. additionwere added
9. stirringthe mixture was stirred for 30 minutes at room temperature
10. temperatureAfter cooling to 0° C.
11. customto rise to room temperature
12. waitAfter 1 h
13. filtrationthe mixture was filtered through Celite
14. customthe solvents were removed in vacuo

ORD record

ord-991804da29da4e51b9e0927b5a165666

Source dataset

uspto-grants-2005_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06846917B2