Sodium Hydroxide → HCID 54275484, compound

HRID 1416439Notes

Reaction equation

HRID 1416439 reaction equation
C([O:4][CH:5]1[CH:9]([N:10]2[C:14]3[CH:15]=[C:16]([Cl:20])[C:17]([Cl:19])=[CH:18][C:13]=3[N:12]=[C:11]2Br)[CH2:8][CH:7]([CH2:22][O:23]C(=O)C)[CH:6]1[O:27]C(=O)C)(=O)C.[CH:31]1([NH2:34])[CH2:33][CH2:32]1.[OH-].[Na+]>C(O)C>[Cl:19][C:17]1[C:16]([Cl:20])=[CH:15][C:14]2[N:10]([CH:9]3[CH:5]([OH:4])[CH:6]([OH:27])[CH:7]([CH2:22][OH:23])[CH2:8]3)[C:11]([NH:34][CH:31]3[CH2:33][CH2:32]3)=[N:12][C:13]=2[CH:18]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 69828CyclopropylamineHCID 54404171HCID 54404171, compound

Product 1

HCID 54275484HCID 54275484, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

(±)(1R*, 2S*, 3R*, 5R*)-3-(Acetoxymethyl)-5-(2-bromo-5,6-dichloro-1H-benzimidazol-1-yl)-1,2-cyclopentanediyl diacetate (Example 39, 1.00 g, 1.87 mmol), cyclopropylamine (Aldrich, 1.7 mL, 24 mmol) and absolute ethanol (10 mL) were refluxed under nitrogen for 48 hours. The reaction was cooled and 1 N sodium hydroxide (1.2 mL) was added. Volatiles were evaporated in vacuo and the residual oily solid was chromatographed on silica gel. Elution with 5% methanol--ethyl acetate gave fractions containing white powder (200 mg). Recrystallization from 1:1 water-ethanol gave (±)-(1R*, 2S*, 3R*, 5R*)-5-[5,6-dichloro-2-(cyclopropylamino)-1H-benzimidazol-1-yl]-3-(hydroxymethyl)-1,2-cyclopentanediol as white crystals (180 mg, 40%); m.p. >250° C.; 1H-NMR(DMSO-d6)δ 7.70 (m, 1, NH), 7.62 and 7.39 (both s, 1 each, 2 benzimidazole CH), 5.77 (br s, 1, OH), 5.13 (d, J=5.3 Hz, 1, OH), 4.95-4.80 (m, 1, CHN), 4.48 (t, J=4.7 Hz, 1, CH2OH), 4.2-4.0 (m, 2, 2 OCH), 3.7-4.0 (m, 2, OCH2), 2.9-2.65 (m, 1, OCH), 2.2-1.8 (m, 3, CH2 and CH); mass spectrum (CI): 372(M+1). [See Examples 10-14]

Workup

  1. temperatureThe reaction was cooled
  2. customVolatiles were evaporated in vacuo
  3. customthe residual oily solid was chromatographed on silica gel
  4. washElution with 5% methanol
  5. customethyl acetate gave fractions
  6. customRecrystallization from 1:1 water-ethanol

Sources & evidence

ORD record
ord-ce3c3231a8bb40449fa3fbde1874d7d1
Source dataset
uspto-grants-1999_06
Patent number
US05912356

Reaction notes

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