Reaction #1951037

Reaction equation

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

sodium methoxide

MeOH H2O

→

4.137

Yield 47.0%

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

Yield 47.0%

Solvents

MeOH

MeOH

Conditions

Workup

1. 1
   Otherwas consumed (TLC)
2. 2
   workup.ADDITIONWater (30 mL) was added
3. 3
   Otherthe solution evaporated until the MeOH
4. 4
   Otherwas completely removed
5. 5
   ExtractionThe residual aqueous suspension was extracted with EtOAc (3×30 mL)
6. 6
   Washthe combined organic extracts washed with brine (20 mL)
7. 7
   Dryingdried over MgSO4
8. 8
   Filtrationfiltered
9. 9
   Otherevaporated
10. 10
    Otherto yield a white solid
11. 11
    workup.ADDITIONFractions containing product
12. 12
    Otherevaporated
13. 13
    Otherto yield a white solid which
14. 14
    Otherwas recrystallized from MeOH and H2O

Procedure

5,6-Dichloro-2-bromo-3-formyl-1-(5-O-acetyl-β-D-ribofuranosyl)indole (4.136, 101 mg, 0.22 mmol) was dissolved in dry MeOH (10 mL) to which was added sodium methoxide (25 mg, 0.46 mmol). The solution was stirred at room temperature for 15 min, until the starting material was consumed (TLC). Water (30 mL) was added and the solution evaporated until the MeOH was completely removed. The residual aqueous suspension was extracted with EtOAc (3×30 mL) and the combined organic extracts washed with brine (20 mL), 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 C18-reverse phase silica gel with 75% MeOH/H2O. Fractions containing product were pooled and evaporated to yield a white solid which was recrystallized from MeOH and H2O to yield 43 mg (47%) of 4.137 as a pale tan powder: mp 210-211° C.; Rf0.2 (10% MeOH/CHCl3); 1H-NMR (500 MHz, DMSO-d6): δ 9.95 (s, 1H), 8.69 (s, 1H), 8.28 (s, 1H), 6.06 (d, 1H), 5.49-5.43 (m, 2H, D2O exch.), 5.31 (d, 1H, D2O exch.), 4.44 (q, 1H), 4.18 (m, 1H), 4.04 (d, 1H), 3.77-3.71 (m, 2H). 13C-NMR (125 MHz, DMSO-d6): δ 185.53, 134.05, 128.85, 126.58, 126.47, 125.31, 120.56, 116.00, 114.68, 90.27, 86.55, 71.69, 69.62, 60.98. HRMS (EI) m/z calcd. for C14H12BrCl2NO5 422.9276, found 422.9271. Anal calcd for C14H12BrCl2NO5: C, 39.56; H, 2.85; N, 3.30. Found: C, 39.77; H, 3.03; N, 3.32.

Source