[(2R,3S,4R,5R)-3,4-dihydroxy-5-(2,5,6-trichloro-3-propanoyl-indol-1-yl)tetrahydrofuran-2-yl]methyl acetate → 1-[2,5,6-trichloro-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]indol-3-yl]propan-1-one

HRID 219537Notes

Reaction equation

HRID 219537 reaction equation
[Cl:1][C:2]1[N:3]([C@@H:17]2[O:23][C@H:22]([CH2:24][O:25]C(=O)C)[C@@H:20]([OH:21])[C@H:18]2[OH:19])[C:4]2[C:9]([C:10]=1[C:11](=[O:14])[CH2:12][CH3:13])=[CH:8][C:7]([Cl:15])=[C:6]([Cl:16])[CH:5]=2.C[O-].[Na+]>CO.CO.C(Cl)(Cl)Cl>[Cl:1][C:2]1[N:3]([C@@H:17]2[O:23][C@H:22]([CH2:24][OH:25])[C@@H:20]([OH:21])[C@H:18]2[OH:19])[C:4]2[C:9]([C:10]=1[C:11](=[O:14])[CH2:12][CH3:13])=[CH:8][C:7]([Cl:15])=[C:6]([Cl:16])[CH:5]=2

Participants

5

Reactant 2

HCID 3012589[(2R,3S,4R,5R)-3,4-dihydroxy-5-(2,5,6-trichloro-3-propanoyl-indol-1-yl)tetrahydrofuran-2-yl]methyl acetateHCID 10942334Sodium Methoxide

Product 1

HCID 30125781-[2,5,6-trichloro-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]indol-3-yl]propan-1-oneYield 198.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 21584188Chloroform methanolSolvent2×

Procedure

2,5,6-Trichloro-3-propionyl-1-(5-O-acetyl-β-D-ribofuranosyl)indole (4.44, 90 mg, 0.21 mmol) was dissolved in dry MeOH (15 mL) to which was added sodium methoxide (14 mg, 0.26 mmol). The solution was stirred at room temperature for 40 min, and the solvent was then removed under vacuum. The residue was suspended in brine (50 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 white 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 boiling EtOAc to yield 170 mg (81%) of 4.47 as a white crystalline solid: mp 239-240 C; Rf 0.3 (10% MeOH/CHCl3); 1H-NMR (500 MHz, DMSO-d6): δ 8.63 (s, 1H), 8.44 (s, 1H), 6.06 (d, 1H), 5.44-5.41 (m, 2H, D2O exch.), 5.29 (d, 1H, D2O exch.), 4.42 (q, 1H), 4.17 (s, 1H), 3.74 (m, 2H), 3.04 (dd, 2H), 1.12 (t, 3H). 13C-NMR (125 MHz, DMSO-d6): δ 195.17, 132.45, 132.41, 126.13, 125.91, 125.84, 122.09, 115.39, 112.60, 88.90, 86.36, 71.58, 69.54, 60.97, 35.05, 7.98. HRMS (EI) m/z calcd. for C16H16Cl3NO5 407.0094. found 407.0089. Anal calcd for C16H16Cl3NO5: C, 47.02; H, 3.95; N, 3.43. Found: C, 46.85; H, 3.96; N, 3.47.

Workup

  1. customthe solvent was then 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 white solid
  7. additionFractions containing product
  8. customevaporated
  9. customto yield a white solid which
  10. customwas recrystallized

Sources & evidence

ORD record
ord-ec9ec149969e42c29148281c35357568
Source dataset
uspto-grants-2012_06
Patent number
US08202844B2

Reaction notes

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