Methanol → 3-(5,6-Dichloro-1H-benzimidazol-1-yl)-1,2-cyclopentanediol

HRID 1734656Notes

Reaction equation

HRID 1734656 reaction equation
[Cl:1][C:2]1[C:15]([Cl:16])=[CH:14][C:5]([NH:6][CH:7]2[CH2:11][CH2:10][CH:9]([OH:12])[CH:8]2[OH:13])=[C:4]([N+:17]([O-])=O)[CH:3]=1.[H][H].CO.[CH:24](Cl)(Cl)Cl>C(O)(C)C.[Ni].C(O)=O>[Cl:1][C:2]1[C:15]([Cl:16])=[CH:14][C:5]2[N:6]([CH:7]3[CH2:11][CH2:10][CH:9]([OH:12])[CH:8]3[OH:13])[CH:24]=[N:17][C:4]=2[CH:3]=1

Participants

8

Reactant 4

HCID 887MethanolHCID 6212ChloroformHCID 67654434HCID 67654434, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 676544263-(5,6-Dichloro-1H-benzimidazol-1-yl)-1,2-cyclopentanediol

Reagents, catalysts & solvents 3

HCID 935NickelCatalystHCID 284Formic AcidSolventHCID 3776IsopropanolSolvent

Procedure

(±)-(1S*, 2R*, 3R*)-3-(4,5-Dichloro-2-nitroanilino)-1,2-cyclopentanediol (3.77 g, 12.3 mmol) in isopropanol (250 mL) was shaken in a Parr shaker with Raney nickel (Aldrich, prewashed with water until neutral, ca. 1 tsp) under hydrogen (50 psi) for 2 hours, at which point uptake of hydrogen had ceased. TLC (silica gel, methanol:chloroform/1:10) shows one spot at lower Rf than starting material. The catalyst was filtered off (Celite) and volatiles evaporated to leave a glass which was refluxed in formic acid (65 mL) for 40 minutes. The formic acid was evaporated and the residual oil dissolved in ethanol (50 mL) and adjusted to pH 13 with 5N sodium hydroxide. After stirring at ambient temperature for 18 hours, the pH was adjusted to 7 with hydrochloric acid and the volatiles removed by evaporation in vacuo. The residue was triturated with methanol. The methanol solution was evaporated to dryness to give white solid which contained product and some salts (7.41 g). A portion of this solid (1.05 g) was chromatographed on silica gel and product was eluted with 6-8% methanol-chloroform as white powder, after solidification from ethanol (350 mg), m.p. 180°-182° C.; 1H-NMR(DMSO-d6)δ: 8.46, 8.08, and 7.93 (all s, 1 each, 3 aromatic CH), 4.96 (d, J=4.7 Hz, 1, OH), 4.92-4.85 (m, 1, NCH), 4.81 (d, J=5.9 Hz, 1, OH), 4.19-4.11 (m, 1, OCH), 4.08-3.93 (m, 1, OCH), 2.38-2.04 (m, 2, CH2), 2.03-1.72 (m, 2, CH2); mass spectrum(CI): 287 (M+1).

Workup

  1. filtrationThe catalyst was filtered off (Celite)
  2. customvolatiles evaporated
  3. customto leave a glass which
  4. customThe formic acid was evaporated
  5. dissolutionthe residual oil dissolved in ethanol (50 mL)
  6. customthe volatiles removed by evaporation in vacuo
  7. customThe residue was triturated with methanol
  8. customThe methanol solution was evaporated to dryness
  9. customto give white solid which
  10. customA portion of this solid (1.05 g) was chromatographed on silica gel and product
  11. washwas eluted with 6-8% methanol-chloroform as white powder

Sources & evidence

ORD record
ord-3a8c9ba0c5764ca288b71ad670dad1f2
Source dataset
uspto-grants-1996_07
Patent number
US05534535

Reaction notes

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