Phenol → HCID 57087935, compound

HRID 1609039Notes

Reaction equation

HRID 1609039 reaction equation
[C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(=O)([O-])[O-].[K+].[K+].C([O:17][C@@H:18]1[C@@H:22]([N:23]2[C:27]3[CH:28]=[C:29]([Cl:33])[C:30]([Cl:32])=[CH:31][C:26]=3[N:25]=[C:24]2Br)[CH2:21][C@@H:20]([CH2:35][O:36]C(=O)C)[C@@H:19]1[O:40]C(=O)C)(=O)C>CN(C)C=O>[Cl:32][C:30]1[C:29]([Cl:33])=[CH:28][C:27]2[N:23]([C@@H:22]3[C@@H:18]([OH:17])[C@@H:19]([OH:40])[C@H:20]([CH2:35][OH:36])[CH2:21]3)[C:24]([O:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[N:25][C:26]=2[CH:31]=1

Participants

5

Reactant 3

HCID 996PhenolHCID 11430Potassium CarbonateHCID 15407222HCID 15407222, compound

Product 1

HCID 57087935HCID 57087935, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Phenol (72 mg, 0.77 mmol) and anhydrous potassium carbonate (106 mg, 0.77 mmol) were stirred in dry N,N-dimethylformamide (5 mL) under nitrogen for 1.0 hour. (±)(1R*,2S*,3S*,5S*)-3-(Acetoxymethyl)-5-(2-bromo-5,6-dichloro-1H-benzimidazol-1-yl)-1,2-cyclopentanediyl diacetate (400 mg, 0.770 mmol) was added and the mixture stirred at 80° C. (oil bath) for 18 hours. Volatiles were removed in vacuo and the residue partitioned between chloroform and water. The chloroform layer was dried (sodium sulfate) and volatiles evaporated. The residual oil was stirred in 4N ammonia in methanol (30 mL) at ambient temperature for 18 hours. Evaporation and chromatography of the residue on silica gel with elution by 2% methanol-chloroform gave (±)-(1R*,2S*,3S*,5S*)-5-(5,6-dichloro-2-phenoxy-1H-benzimidazol-1-yl)-3-(hydroxymethyl)-1,2-cyclopentanediol as white solid foam from ethyl acetate (215 mg, 68%); 1H-NMR(DMSO-d6) δ: 7.98 and 7.71 (both s, 2, aromatic CH), 7.6-7.3 (m, 5, C6H5), 5.07 (d, J=6.4 Hz, 1, OH), 5.0-4.75 (m overlapping t at 4.95, J=3.1 Hz, total 2, NCH and OH), 4.71 (d, J=3.9 Hz, 1, OH), 4.5-4.35 (m, 1, OCH), 3.9-3.8 (m, 1, OCH), 3.7-3.4 (m, 2, OCH2), 2.3-1.9 (m, 3, CH2 and CH); mass spectrum (CI): 409 (M+1).

Workup

  1. customVolatiles were removed in vacuo
  2. customthe residue partitioned between chloroform and water
  3. dry with materialThe chloroform layer was dried (sodium sulfate)
  4. customvolatiles evaporated
  5. stirringThe residual oil was stirred in 4N ammonia in methanol (30 mL) at ambient temperature for 18 hours
  6. customEvaporation and chromatography of the residue on silica gel
  7. washwith elution by 2% methanol-chloroform

Sources & evidence

ORD record
ord-f51052137ab0425eb831edc527aba506
Source dataset
uspto-grants-1995_03
Patent number
US05399580

Reaction notes

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