[(2R,3S,4R,5R)-5-(2-bromo-5,6-dichloro-3-formyl-indol-1-yl)-3,4-dihydroxy-tetrahydrofuran-2-yl]methyl acetate → 2-bromo-5,6-dichloro-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]indole-3-carbaldehyde

HRID 28365Notes

Reaction equation

HRID 28365 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[Cl:11])[N:7]([C@@H:12]1[O:18][C@H:17]([CH2:19][O:20]C(=O)C)[C@@H:15]([OH:16])[C@H:13]1[OH:14])[C:6]([Br:24])=[C:5]2[CH:25]=[O:26].C[O-].[Na+].CO.O>CO>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[Cl:11])[N:7]([C@@H:12]1[O:18][C@H:17]([CH2:19][OH:20])[C@@H:15]([OH:16])[C@H:13]1[OH:14])[C:6]([Br:24])=[C:5]2[CH:25]=[O:26]

Participants

5

Reactant 3

HCID 3012593[(2R,3S,4R,5R)-5-(2-bromo-5,6-dichloro-3-formyl-indol-1-yl)-3,4-dihydroxy-tetrahydrofuran-2-yl]methyl acetateHCID 10942334Sodium MethoxideHCID 22242641Methanol--water (1/1)

Product 1

HCID 30125862-bromo-5,6-dichloro-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]indole-3-carbaldehydeYield 47%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

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.; Rf 0.2 (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.

Workup

  1. customwas consumed (TLC)
  2. additionWater (30 mL) was added
  3. customthe solution evaporated until the MeOH
  4. customwas completely removed
  5. extractionThe residual aqueous suspension was extracted with EtOAc (3×30 mL)
  6. washthe combined organic extracts washed with brine (20 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customevaporated
  10. customto yield a white solid
  11. additionFractions containing product
  12. customevaporated
  13. customto yield a white solid which
  14. customwas recrystallized from MeOH and H2O

Sources & evidence

ORD record
ord-9b7045e2c9d54a7d861b42c828d0fa29
Source dataset
uspto-grants-2008_09
Patent number
US07419963B2

Reaction notes

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