Reaction #56626

Reaction equation

MeOH CHCl3

MeOH H2O

sodium methoxide

2,5,6-Trichloro-3-formyl-1-(5-O-acetyl-β-D-ribofuranosyl)indole

→

4.25

Yield 42.0%

5,6-Dichloro-2-methoxy-3-formyl-1-(β-D-ribofuranosyl)indole

Yield 42.0%

Solvents

MeOH

MeOH

MeOH

Conditions

Workup

1. 1
   Otherthe solvent was removed under vacuum
2. 2
   Extractionthe suspension extracted with EtOAc (2×50 mL)
3. 3
   DryingThe combined organic extracts were dried over MgSO4
4. 4
   Filtrationfiltered
5. 5
   Otherevaporated
6. 6
   Otherto yield a white solid
7. 7
   workup.ADDITIONFractions containing product
8. 8
   Otherevaporated
9. 9
   Otherto yield a white solid (the balance of recovered material
10. 10
    workup.ADDITIONFractions containing product
11. 11
    Otherevaporated

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.

Source