[(2R,3S,4R,5R)-3,4-dihydroxy-5-(2,5,6-trichloro-3-formyl-indol-1-yl)tetrahydrofuran-2-yl]methyl acetate → HCID 11523673, compound

HRID 28348Notes

Reaction equation

HRID 28348 reaction equation
Cl[C:2]1[N:3]([C@@H:15]2[O:21][C@H:20]([CH2:22][O:23]C(=O)C)[C@@H:18]([OH:19])[C@H:16]2[OH:17])[C:4]2[C:9]([C:10]=1[CH:11]=[O:12])=[CH:8][C:7]([Cl:13])=[C:6]([Cl:14])[CH:5]=2.[CH3:27][O-:28].[Na+].CO.C(Cl)(Cl)Cl.CO.O>CO>[Cl:13][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][C:6]=1[Cl:14])[N:3]([C@@H:15]1[O:21][C@H:20]([CH2:22][OH:23])[C@@H:18]([OH:19])[C@H:16]1[OH:17])[C:2]([O:28][CH3:27])=[C:10]2[CH:11]=[O:12]

Participants

6

Reactant 4

HCID 3012567[(2R,3S,4R,5R)-3,4-dihydroxy-5-(2,5,6-trichloro-3-formyl-indol-1-yl)tetrahydrofuran-2-yl]methyl acetateHCID 10942334Sodium MethoxideHCID 21584188Chloroform methanolHCID 22242641Methanol--water (1/1)

Product 1

HCID 11523673HCID 11523673, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent3×

Procedure

2,5,6-Trichloro-3-formyl-1-(5-O-acetyl-β-D-ribofuranosyl)indole (see Chen et al.; 4.24, 148 mg, 0.35 mmol) was dissolved in dry MeOH (20 mL) to which was added sodium methoxide (21 mg, 0.39 mmol). The solution was stirred at room temperature for 30 min, then the solvent was removed under vacuum. The residue was suspended in 10% aqueous NaHCO3, and the suspension extracted with EtOAc (2×50 mL). The combined organic extracts were dried over MgSO4, filtered and evaporated to yield a white solid. The solid was dissolved in MeOH (1 mL) and subjected to column chromatography (40×350 mm) on silica gel with 20% MeOH/CHCl3. Fractions containing product were pooled and evaporated to yield a white solid (the balance of recovered material was the deprotected 2-chloro derivative). The crude product was dissolved in MeOH and subjected to column chromatography (40×350 mm) on C18-reverse phase silica gel with 75% MeOH/H2O. Fractions containing product were pooled and evaporated to yield 50 mg (42%) of 4.25 as a white crystalline solid: mp 198-199° C.; Rf 0.2 (10% MeOH/CHCl3); 1H-NMR (500 MHz, DMSO-d6): δ 10.21 (s, 1H), 8.34 (s, 1H), 8.31 (s, 1H), 5.84 (d, 1H), 5.41 (d, 1H, D2O exch.), 5.30 (t, 1H, D2O exch.), 5.23 (d, 1H, D2O exch.), 4.41 (s, 4H), 4.13 (s, 1H), 3.95 (d, 1H), 3.69 (m, 2H). 13C-NMR (125 MHz, DMSO-d6): δ 183.28, 160.04, 129.51, 125.21, 124.83, 124.68, 121.12, 114.73, 100.30, 86.81, 85.93, 71.06, 69.75, 64.78, 61.18. HRMS (EI) m/z calcd. for C15H15Cl2NO6 375.0276, found 375.0278. Anal calcd for C15H15Cl2NO6: C, 47.89; H, 4.02; N, 3.72. Found: C, 47.73; H, 4.12; N, 3.72.

Workup

  1. customthe solvent was removed under vacuum
  2. extractionthe suspension extracted with EtOAc (2×50 mL)
  3. dry with materialThe combined organic extracts were dried over MgSO4
  4. filtrationfiltered
  5. customevaporated
  6. customto yield a white solid
  7. additionFractions containing product
  8. customevaporated
  9. customto yield a white solid (the balance of recovered material
  10. additionFractions containing product
  11. customevaporated

Sources & evidence

ORD record
ord-47a21cea69294e17bd51450df6c572f5
Source dataset
uspto-grants-2008_09
Patent number
US07419963B2

Reaction notes

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