Sodium Methoxide → (2R,3S,5R)-2-(hydroxymethyl)-5-[2,5,6-trichloro-3-(2-furyl)indol-1-yl]tetrahydrofuran-3-ol

HRID 28362Notes

Reaction equation

HRID 28362 reaction equation
[Cl:1][C:2]1[N:3]([C@@H:18]2[O:32][C@H:31]([CH2:33][O:34]C(C3C(C)=CC=CC=3)=O)[C@@H:20]([O:21]C(C3C(C)=CC=CC=3)=O)[CH2:19]2)[C:4]2[C:9]([C:10]=1[C:11]1[O:12][CH:13]=[CH:14][CH:15]=1)=[CH:8][C:7]([Cl:16])=[C:6]([Cl:17])[CH:5]=2.C[O-].[Na+].CO.C(Cl)(Cl)Cl>CO.C(Cl)(Cl)Cl>[Cl:1][C:2]1[N:3]([C@@H:18]2[O:32][C@H:31]([CH2:33][OH:34])[C@@H:20]([OH:21])[CH2:19]2)[C:4]2[C:9]([C:10]=1[C:11]1[O:12][CH:13]=[CH:14][CH:15]=1)=[CH:8][C:7]([Cl:16])=[C:6]([Cl:17])[CH:5]=2

Participants

6

Reactant 3

HCID 10942334Sodium MethoxideHCID 21584188Chloroform methanolHCID 670990502,5,6-Trichloro-3-(2-furyl)-1-(3,5-di-O-toluoyl-2-deoxy-beta-D-ribofuranosyl)indole

Product 1

HCID 5273006(2R,3S,5R)-2-(hydroxymethyl)-5-[2,5,6-trichloro-3-(2-furyl)indol-1-yl]tetrahydrofuran-3-olYield 75.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

2,5,6-Trichloro-3-(2-furyl)-1-(3,5-di-O-toluoyl-2-deoxy-β-D-ribofuranosyl)indole (4.76, 142 mg, 0.22 mmol) was suspended in dry MeOH (10 mL) to which was added sodium methoxide (30 mg, 0.56 mmol). The suspension was stirred at room temperature for 45 min, until the solids were completely dissolved. The solvent was then removed under vacuum, and the residue suspended in brine (50 mL). The aqueous suspension was extracted with EtOAc (2×50 mL), and the combined organic extracts were dried over MgSO4, filtered and evaporated to yield a clear oil. The oil was dissolved in 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 pale yellow solid which was recrystallized from 10% MeOH/CHCl3 and hexane to yield 67 mg (75%) of 4.78 as a white crystalline solid: mp 140-141 C; Rf 0.5 (10% MeOH/CHCl3); 1H-NMR (500 MHz, DMSO-d6): δ 8.46 (s, 1H), 8.14 (s, 1H), 7.86 (s, 1H), 6.88 (d, 1H), 6.68 (s, 1H), 6.47 (dd, 1H), 5.42 (d, 1H, D2O exch.), 5.23 (s, 1H, D2O exch.), 4.45 (d, 1H), 3.89 (d, 1H), 3.73 (s, 2H), 2.55 (m, 1H), 2.13 (m, 1H). 13C-NMR (125 MHz, DMSO-d6): δ 146.54, 142.25, 132.30, 125.61, 124.39, 124.09, 122.64, 120.75, 114.98, 111.51, 106.91, 104.87, 87.25, 85.04, 69.98, 60.91, 38.97. HRMS (EI) m/z calcd. for C17H14Cl3NO4 400.9988, found 400.9986. Anal calcd for C17H14Cl3NO4·¼H2O: C, 50.15; H, 3.59; N, 3.44. Found: C, 50.17; H, 3.65; N, 3.43.

Workup

  1. dissolutionwere completely dissolved
  2. customThe solvent was then removed under vacuum
  3. extractionThe aqueous suspension was extracted with EtOAc (2×50 mL)
  4. dry with materialthe combined organic extracts were dried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customto yield a clear oil
  8. additionFractions containing product
  9. customevaporated
  10. customto yield a pale yellow solid which
  11. customwas recrystallized from 10% MeOH/CHCl3 and hexane

Sources & evidence

ORD record
ord-5ea0b38ee221485191ef5994d6a4a20e
Source dataset
uspto-grants-2008_09
Patent number
US07419963B2

Reaction notes

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