Acetic Acid → 2-Amino-2-[6-(2,2-dimethylpropyl)-1H-benzimidazol-2-yl]propan-1-ol

HRID 1424156Notes

Reaction equation

HRID 1424156 reaction equation
C(OC([NH:8][C:9]([CH3:15])([CH2:13][OH:14])[C:10](O)=O)=O)(C)(C)C.CN1CCOCC1.C(OC(Cl)=O)C(C)C.[CH2:31]([C:36]1[CH:37]=[C:38]([NH2:43])[C:39]([NH2:42])=[CH:40][CH:41]=1)[C:32]([CH3:35])([CH3:34])[CH3:33].C(O)(=O)C.FC(F)(F)C(O)=O>C(#N)C>[NH2:8][C:9]([C:10]1[NH:43][C:38]2[CH:37]=[C:36]([CH2:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH:41]=[CH:40][C:39]=2[N:42]=1)([CH3:15])[CH2:13][OH:14]

Participants

8

Reactant 6

HCID 176Acetic AcidHCID 6422Trifluoroacetic acidHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 132218752-{[(Tert-butoxy)carbonyl]amino}-3-hydroxy-2-methylpropanoic acidHCID 866990534-Neopentylbenzene-1,2-diamine

Product 1

HCID 866990522-Amino-2-[6-(2,2-dimethylpropyl)-1H-benzimidazol-2-yl]propan-1-olYield 10.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 2-((tert-butoxycarbonyl)amino)-3-hydroxy-2-methylpropanoic acid (Preparation 53, 186 mg, 0.85 mmol) acetonitrile (4.0 mL) and 4-methylmorpholine (0.15 mL, 1.4 mmol) cooled in an ice/brine bath was added isobutylchloroformate (0.050 mL, 0.38 mmol). The mixture was stirred for 30 minutes and then 4-neopentylbenzene-1,2-diamine (Preparation 83, 139 mg, 0.78 mmol) was added. The reaction mixture was allowed to warm to room temperature and stir for 4 days. The solvent was evaporated and the resulting oil was dissolved in acetic acid (3.0 mL, 50 mmol) and stirred at room temperature for 16 hours and then heated to 70° C. for 5 hours. After cooling, the solvent was removed in vacuo and the residue purified by silica gel column chromatography eluting with a 0-100% ethyl acetate/hexanes gradient. The resulting oil was dissolved in methylene chloride (5 mL) and treated with trifluoroacetic acid (0.5 mL, 6 mmol). After stirring for 2 hours, the reaction mixture was concentrated in vacuo and purified by silica gel column chromatography eluting with a 0-100% CMA80/methylene chloride gradient to provide the title compound (20.6 mg, 10%) as an off-white solid.

Workup

  1. stirringstir for 4 days
  2. customThe solvent was evaporated
  3. stirringstirred at room temperature for 16 hours
  4. temperatureheated to 70° C. for 5 hours
  5. temperatureAfter cooling
  6. customthe solvent was removed in vacuo
  7. customthe residue purified by silica gel column chromatography
  8. washeluting with a 0-100% ethyl acetate/hexanes gradient
  9. dissolutionThe resulting oil was dissolved in methylene chloride (5 mL)
  10. stirringAfter stirring for 2 hours
  11. concentrationthe reaction mixture was concentrated in vacuo
  12. custompurified by silica gel column chromatography
  13. washeluting with a 0-100% CMA80/methylene chloride gradient

Sources & evidence

ORD record
ord-2d3267f381584085836818ea32c4e335
Source dataset
uspto-grants-2015_01
Patent number
US08927587B2

Reaction notes

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