Sodium Methoxide → 5,6-Dichloro-1-(4-hydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-2-methoxy-1H-indole-3-carbaldehyde

HRID 2076786Notes

Reaction equation

HRID 2076786 reaction equation
[CH:1]([C:3]1[C:11]2[C:6](=[CH:7][C:8]([Cl:13])=[C:9]([Cl:12])[CH:10]=2)[N:5]([C@@H:14]2[O:28][C@H:27]([CH2:29][O:30]C(C3C=CC(C)=CC=3)=O)[C@@H:16]([O:17]C(C3C=CC(C)=CC=3)=O)[CH2:15]2)[C:4]=1Cl)=[O:2].[CH3:41][O-:42].[Na+].CO.C(Cl)(Cl)Cl>CO>[Cl:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][C:8]=1[Cl:13])[N:5]([C@@H:14]1[O:28][C@H:27]([CH2:16][OH:17])[C@@H:29]([OH:30])[CH2:15]1)[C:4]([O:42][CH3:41])=[C:3]2[CH:1]=[O:2]

Participants

5

Reactant 3

HCID 10942334Sodium MethoxideHCID 21584188Chloroform methanolHCID 872687613-Formyl-2,5,6-trichloro-1-[3,5-di-o-(p-toluoyl)-2-deoxy-beta-d-ribofuranosyl]indole

Product 1

HCID 52726185,6-Dichloro-1-(4-hydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-2-methoxy-1H-indole-3-carbaldehydeYield 69%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

3-Formyl-2,5,6-trichloro-1-[3,5-di-O-(p-toluoyl)-2-deoxy-β-D-ribofuranosyl]indole (4.113, 198 mg, 0.33 mmol) was suspended in dry MeOH (10 mL) to which was added sodium methoxide (75 mg, 1.4 mmol). The suspension was stirred at room temperature for 16 h, after which time the solution clarified. The solvent was then removed under vacuum, and the residue was suspended in water (50 mL), and extracted with EtOAc (2×100 mL). The combined organic extracts were washed with brine (25 mL), dried over MgSO4, filtered and evaporated to yield a damp solid. The crude material was dissolved in MeOH (1 mL) and subjected to column chromatography (40×350 mm) on silica gel with 10% MeOH/CHCl3. Fractions containing product were pooled and evaporated to yield a white solid. The solid was recrystallized from warm MeOH to yield 82 mg (68%) of 4.114 as a white crystalline solid: mp 186-187° C.; Rf 0.3 (10% MeOH/CHCl3); 1H-NMR (500 MHz, DMSO-d6): δ 10.21 (s, 1H), 8.29 (s, 1H), 8.22 (s, 1H), 6.32 (dd, 1H), 5.37 (b, 1H, D2O exch.), 5.15 (b, 1H, D2O exch.), 4.43 (s, 3H), 4.41 (m, 1H), 3.83 (d, 1H), 3.68 (m, 2H), 2.53 (m, 1H), 2.11 (m, 1H). 13C-NMR (125 MHz, DMSO-d6): δ 183.22, 159.16, 129.40, 125.04, 124.73, 124.66, 121.11, 114.24, 100.02, 87.29, 82.99, 70.07, 64.16, 61.03, 38.43. HRMS (EI) m/z calcd. for C15H15Cl2NO5 359.0327, found 359.0320. Anal calcd for C15H15Cl2NO5.½ H2O: C, 48.80; H, 4.37; N, 3.79. Found: C, 48.48; H, 4.61; N, 3.61.

Workup

  1. customThe solvent was then removed under vacuum
  2. extractionextracted with EtOAc (2×100 mL)
  3. washThe combined organic extracts were washed with brine (25 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customto yield a damp solid
  8. additionFractions containing product
  9. customevaporated
  10. customto yield a white solid
  11. customThe solid was recrystallized
  12. temperaturefrom warm MeOH

Sources & evidence

ORD record
ord-1bbc95779ef44f44a33d1d9068fc51c3
Source dataset
uspto-grants-2011_04
Patent number
US07928080B2

Reaction notes

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