Sodium Methoxide → HCID 3012579, compound

HRID 219538Notes

Reaction equation

HRID 219538 reaction equation
[Cl:1][C:2]1[N:3]([C@@H:19]2[O:25][C@H:24]([CH2:26][O:27]C(=O)C)[C@@H:22]([OH:23])[C@H:20]2[OH:21])[C:4]2[C:9]([C:10]=1[C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])=[CH:8][C:7]([Cl:17])=[C:6]([Cl:18])[CH:5]=2.C[O-].[Na+]>CO.CO.C(Cl)(Cl)Cl>[Cl:1][C:2]1[N:3]([C@@H:19]2[O:25][C@H:24]([CH2:26][OH:27])[C@@H:22]([OH:23])[C@H:20]2[OH:21])[C:4]2[C:9]([C:10]=1[C:11](=[O:16])[C:12]([F:13])([F:14])[F:15])=[CH:8][C:7]([Cl:17])=[C:6]([Cl:18])[CH:5]=2

Participants

5

Reactant 2

HCID 10942334Sodium MethoxideHCID 11386307HCID 11386307, compound

Product 1

HCID 3012579HCID 3012579, compoundYield 56.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 21584188Chloroform methanolSolvent2×

Procedure

2,5,6-Trichloro-3-trifluoroacetyl-1-(5-O-acetyl-β-D-ribofuranosyl)indole (4.45, 94 mg, 0.19 mmol) was dissolved in dry MeOH (20 mL) to which was added sodium methoxide (12 mg, 0.22 mmol). The solution was stirred at room temperature for 90 min, then the solvent was removed under vacuum. The residue was suspended in brine (40 mL) and water (5 mL), and the suspension extracted with EtOAc (2×50 mL). The combined organic extracts were dried over MgSO4, filtered and evaporated to yield a yellow-orange solid. The solid was dissolved in 10% MeOH/CHCl3 (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 which was recrystallized from MeOH/H2O to yield 48 mg (56%) of 4.48 as a pale yellow powder: mp 179-180 C; Rf 0.3 (10% MeOH/CHCl3); 1H-NMR (500 MHz, DMSO-d6): δ 8.80 (s, 1H), 8.23 (s, 1H), 6.14 (d, 1H), 5.50 (b, 2H, D2O exch.), 5.34 (b, 1H, D2O exch.), 4.44 (t, 1H), 4.19 (dd, 1H), 4.06 (d, 1H), 3.76 (dq, 2H). 13C-NMR (125 MHz, DMSO-d6): δ 173.47 (J=37 Hz), 132.34, 132.65, 127.38, 127.28, 125.47, 121.35, 116.29, 115.88 (J=289 Hz), 106.90, 89.42, 86.88, 71.96, 69.49, 60.86. 19F-NMR (300 MHz, DMSO-d6): δ −72.34. HRMS (EI) m/z calcd. for C15H11Cl3F3NO5 446.9655. found 446.9661. Anal calcd for C15H11Cl3F3NO5: C, 40.16; H, 2.47; N, 3.12. Found: C, 40.18; H, 2.60; N, 2.98.

Workup

  1. customthe solvent was removed under vacuum
  2. extractionwater (5 mL), and the 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 yellow-orange solid
  7. additionFractions containing product
  8. customevaporated
  9. customto yield a white solid which
  10. customwas recrystallized from MeOH/H2O

Sources & evidence

ORD record
ord-2624780a25534ff7a680de4da664e006
Source dataset
uspto-grants-2012_06
Patent number
US08202844B2

Reaction notes

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