Sodium Bicarbonate → 2,5,6-Trichloro-3-(N-methoxyiminomethylidene)-1-(beta-D-ribofuranosyl)indole

HRID 28351

Reaction equation

HRID 28351 reaction equation
[Cl:1][C:2]1[N:3]([C@@H:15]2[O:21][C@H:20]([CH2:22][OH:23])[C@@H:18]([OH:19])[C@H:16]2[OH:17])[C:4]2[C:9]([C:10]=1[CH:11]=O)=[CH:8][C:7]([Cl:13])=[C:6]([Cl:14])[CH:5]=2.Cl.[O:25]([NH2:27])[CH3:26].C(=O)(O)[O-].[Na+].CO.O>CO.O.S([O-])([O-])(=O)=S.[Na+].[Na+]>[Cl:1][CH:2]1[C:10](=[C:11]=[N:27][O:25][CH3:26])[C:9]2[C:4](=[CH:5][C:6]([Cl:14])=[C:7]([Cl:13])[CH:8]=2)[N:3]1[C@@H:15]1[O:21][C@H:20]([CH2:22][OH:23])[C@@H:18]([OH:19])[C@H:16]1[OH:17]

Participants

8

Reactant 4

HCID 516892Sodium BicarbonateHCID 521874O-Methylhydroxylamine hydrochlorideHCID 3011610FtcriHCID 22242641Methanol--water (1/1)

Product 1

HCID 865989692,5,6-Trichloro-3-(N-methoxyiminomethylidene)-1-(beta-D-ribofuranosyl)indoleYield 41%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 24477Sodium ThiosulfateSolvent

Procedure

To a solution of 2,5,6-trichloro-3-formyl-1-(β-D-ribofuranosyl)indole (4.3, 103 mg, 0.27 mmol) in MeOH (5 mL) was added a solution of methoxylamine hydrochloride (27 mg, 0.32 mmol) and sodium bicarbonate (22 mg, 0.26 mmol) in water (1.0 mL). The resulting mixture was stirred at room temperature for 16 h, then the solvent was evaporated to provide a pale yellow residue. The residue was suspended in 10 mL of 5% aqueous sodium thiosulfate and extracted with EtOAc (2×25 mL). The combined organic extracts were washed with brine (10 mL), dried over MgSO4, filtered and evaporated to yield a yellow residue. The residue was subjected to column chromatography (40×350 mm) on C18 reverse-phase silica gel with 80% MeOH/H2O. The appropriate UV-active fractions were pooled and evaporated to yield a white powder. The powder was recrystallized from Et2O to yield 45 mg (41%) of 4.30 as a white crystalline solid: mp 197-198 C; Rf 0.4 (10% MeOH/CHCl3); 1H NMR (500 MHz, DMSO-d6) δ 8.57 (s, 1H), 8.27 (s, 1H), 8.17 (s, 1H), 5.93 (d, 1H), 5.42 (d, 1H, D2O exch.), 5.40 (t, 1H, D2O exch.), 5.27 (d, 1H, D2O exch.), 4.42 (q, 1H), 4.14 (m, 1H), 4.00 (d, 1H), 3.96 (s, 3H), 3.71 (m, 2H). 13C NMR (125 MHz, DMSO-d6) δ 141.84, 133.04, 129.74, 126.09, 125.03, 123.82, 121.70, 115.46, 105.59, 88.85, 86.13, 71.43, 69.65, 61.84, 61.09. HRMS (EI) m/z calcd. for C15H15Cl3N2O5 408.0047, found 408.0047. Anal calcd for C15H15Cl3N2O5: C, 43.98; H, 3.69; N, 6.84. Found: C, 43.79; H, 3.68; N, 6.61.

Workup

  1. customthe solvent was evaporated
  2. customto provide a pale yellow residue
  3. extractionextracted with EtOAc (2×25 mL)
  4. washThe combined organic extracts were washed with brine (10 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customto yield a yellow residue
  9. customevaporated
  10. customto yield a white powder
  11. customThe powder was recrystallized from Et2O

Sources & evidence

ORD record
ord-86df222567724b65ab14bc1c8fb7ccd5
Source dataset
uspto-grants-2008_09
Patent number
US07419963B2

Linked notes

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