Acetic Anhydride → HCID 86748565, compound

HRID 1734639Notes

Reaction equation

HRID 1734639 reaction equation
[Cl:1][C:2]1[C:17]([Cl:18])=[CH:16][C:5]2[N:6]([C@@H:9]3[CH2:13][C@H:12]([CH2:14][OH:15])[CH:11]=[CH:10]3)[CH:7]=[N:8][C:4]=2[CH:3]=1.C(OC(=O)C)(=O)C.[Br:26]N1C(=O)CCC1=O>N1C=CC=CC=1>[Br:26][C:7]1[N:6]([C@@H:9]2[CH2:13][C@H:12]([CH2:14][OH:15])[CH:11]=[CH:10]2)[C:5]2[CH:16]=[C:17]([Cl:18])[C:2]([Cl:1])=[CH:3][C:4]=2[N:8]=1

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 67184N-bromobutanimideHCID 86748564HCID 86748564, compound

Product 1

HCID 86748565HCID 86748565, compoundYield 14.8%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

(±)-cis-[4-(5,6-Dichloro-1H-benzimidazol-1-yl)-2-cyclopenten-1-yl]methanol (1.55 g, 5.47 mmol) was acetylated in pyridine (17 mL) with acetic anhydride (0.6 mL) at ambient temperature for 2 days. Volatiles were removed in vacuo and the residual oil partitioned between chloroform and aqueous sodium bicarbonate. The chloroform solution was dried (sodium sulfate) and concentrated to dryness. The residue was dissolved in dry dioxane (10 mL) and the solution brought to reflux. N-bromosuccinimide (930 mg, 5.23 mmol) was added all at once. The dark solution was cooled after 4 minutes of reflux. Volatiles were evaporated in vacuo and the residue was chromatographed on silica gel. Elution with 2-5% methanol-chloroform gave fractions containing starting material (1.05 g) followed by fractions containing title compound as a dark oil (0.28 g). The recovered starting material was again treated with N-bromosuccinimide and the crude product chromatographed. All product-containing fractions were combined and rechromatographed on silica gel with elution by hexanes-ethyl acetate to give the acetate of title compound as a yellow oil (0.62 g). Deacetylation was carried out as in Example 4. Volatiles were evaporated in vacuo from the neutralized solution and the residue was chromatographed on silica gel. Elution with 2% methanol-chloroform gave (±)-cis-[4-(2-bromo-5,6-dichloro-1H-benzimidazol-1-yl)-2-cyclopenten-1-yl]methanol as off-white powder (293 mg, 15%), after resolidification from hexanes-ethyl acetate, m.p. 126°-128.5° C.; 1H-NMR(DMSO-d6)δ: 8.09 and 7.95 (both s, 1 each, aromatic CH), 6.24-6.20 and 5.98-5.94 (both m, 2, CH=CH), 5.81-5.76 (2 m, 1 each, CH2O), 4.96 (t, J=4.9 Hz, 1, OH), 3.02-2.95 (m, 1, CH), 2.67-2.51 (m overlapping solvent, 1/2CH2), 2.0-1.8 (m, 1, 1/2CH2); mass spectrum (CI) consistent with structure.

Workup

  1. customVolatiles were removed in vacuo
  2. customthe residual oil partitioned between chloroform and aqueous sodium bicarbonate
  3. dry with materialThe chloroform solution was dried (sodium sulfate)
  4. concentrationconcentrated to dryness
  5. dissolutionThe residue was dissolved in dry dioxane (10 mL)
  6. temperatureto reflux
  7. temperatureThe dark solution was cooled after 4 minutes
  8. temperatureof reflux
  9. customVolatiles were evaporated in vacuo
  10. customthe residue was chromatographed on silica gel
  11. washElution with 2-5% methanol-chloroform
  12. customgave fractions

Sources & evidence

ORD record
ord-f0899a5084854749bcc0d67e20d106b9
Source dataset
uspto-grants-1996_07
Patent number
US05534535

Reaction notes

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