Isopropanol → HCID 20083551, compound

HRID 1734644Notes

Reaction equation

HRID 1734644 reaction equation
C([O:4][CH:5]1[CH:9]([NH:10][C:11]2[CH:16]=[C:15]([Cl:17])[C:14]([Cl:18])=[CH:13][C:12]=2[N+:19]([O-])=O)[CH2:8][CH:7]([CH2:22][O:23]C(=O)C)[CH:6]1[O:27]C(=O)C)(=O)C.[CH:31](O)(C)[CH3:32]>[Ni]>[Cl:18][C:14]1[C:15]([Cl:17])=[CH:16][C:11]2[N:10]([CH:9]3[CH:5]([OH:4])[CH:6]([OH:27])[CH:7]([CH2:22][OH:23])[CH2:8]3)[C:31]([CH3:32])=[N:19][C:12]=2[CH:13]=1

Participants

4

Reactant 2

HCID 3776IsopropanolHCID 54275101HCID 54275101, compound

Product 1

HCID 20083551HCID 20083551, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 935NickelCatalyst

Procedure

(±)-(1R*, 2S*, 3S*, 5S*)-3-(Acetoxymethyl)-5-(4,5-dichloro-2-nitroanilino)-1,2-cyclopentanediyl diacetate (1.00 g, 2.16 mmol), Raney nickel (Aldrich, slurry in water, 100 mg wet), and isopropanol (200 mL) were shaken under hydrogen (50 psi) for 1.25 hours. Catalyst was filtered off with Celite and the filtrate-wash evaporated to dryness. The residual yellow oil was dissolved in triethylorthoaceate (20 mL) with 1 drop of methanesulfonic acid and the solution stirred at ambient temperature for 18 hours. Volatiles were removed in vacuo and the residue stirred in dioxane (20 mL)-1N sodium hydroxide (10 mL) for 5 hours at ambient temperature. The pH was then adjusted to 1 with concentrated hydrochloric acid and stirring continued for 15 minutes, at which point TLC (silica gel, developed with 20% methanol-chloroform) showed one UV-absorbing spot at Rf 0.25. The solution was neutralized with sodium hydroxide and volatiles evaporated in vacuo. The residue was chromatographed on a silica gel column and title compound eluted with 10-15% methanol-chloroform. Crystallization from ethanol-methanol-water gave (±)-(1R*, 2S*, 3S*, 5S*)-5-(5,6-dichloro-2-methyl-1H-benzimidazol-1-yl)-3-(hydroxymethyl)-1,2-cyclopentanediol as fine white crystals (0.482 g, 67%), m.p. 222°-226° C.; 1 H-NMR(DMSO-d6)δ: 8.30 and 7.72 (both s, 2, 2 aromatic CH), 5.0-4.8 (m, 3, 2 OH and NCH), 4.56 (t, J=5.1 Hz, 1, CH2OH), 4.2-4.1 (m, 2, 2 OCH), 3.8-3.5 (m, 2, CH2O), 2.58 (s, 3, CH3), 2.4-2.2 (m, 1, CH), 2.2-1.9 (m, 2, CH2); mass spectrum (CI): 332 (M +1).

Workup

  1. filtrationCatalyst was filtered off with Celite
  2. customthe filtrate-wash evaporated to dryness
  3. dissolutionThe residual yellow oil was dissolved in triethylorthoaceate (20 mL) with 1 drop of methanesulfonic acid
  4. customVolatiles were removed in vacuo
  5. stirringthe residue stirred in dioxane (20 mL)-1N sodium hydroxide (10 mL) for 5 hours at ambient temperature
  6. stirringstirring
  7. waitcontinued for 15 minutes, at which point TLC (silica gel, developed with 20% methanol-chloroform)
  8. customevaporated in vacuo
  9. customThe residue was chromatographed on a silica gel column and title compound
  10. washeluted with 10-15% methanol-chloroform
  11. customCrystallization from ethanol-methanol-water

Sources & evidence

ORD record
ord-ddcbbacbd64b4390a5276e95afeab344
Source dataset
uspto-grants-1996_07
Patent number
US05534535

Reaction notes

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