2,2,2-Trifluoroethanol → HCID 70148112, compound

HRID 2230737Notes

Reaction equation

HRID 2230737 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[N:19]([CH2:20][CH2:21]OS(C)(=O)=O)[C:18]3[CH:27]=[CH:28][CH:29]=[CH:30][C:17]=3[N:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].FC(F)(F)CO.O1CCCC1.[H-].[Na+]>CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[N:19]([CH:20]=[CH2:21])[C:18]3[CH:27]=[CH:28][CH:29]=[CH:30][C:17]=3[N:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 64092,2,2-TrifluoroethanolHCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 18464661HCID 18464661, compound

Product 1

HCID 70148112HCID 70148112, compoundYield 102.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-(1-Vinyl-1H-benzoimidazol-2-yl)-[1,4]diazepane-1-carboxylic acid tert-butyl ester is the major product obtained from an alternative synthesis of 1-(2,2,2-trifluoroethoxy)ethyl)-1H-benzimidazol-2-yl)-[1,4]diazepane (Preparation 44.2). Treat a stirred solution of 1-(t-butoxycarbonyl)-4-(1-(2-methanesulfonyloxyethyl)-1H-benzimidazol-2-yl)-[1,4]diazepane (1.21 g, 2.77 mmol, Preparation 9), 2,2,2-trifluoroethanol (2.75 g, 27.4 numol, Aldrich Chemical Company), anhydrous tetrahydrofuran (20 mL) and dimethylformamide (2 mL) at 0-5° C. with sodium hydride (0.44 g, 11 mmol, 60% oil dispersion) under an argon atmosphere. Stir overnight at room temperature, heat at 50° C. for four hours, and stir at room temperature for two hours. Cool to 0° C., quench by addition of saturated ammonium chloride solution (5 mL) and concentrate in vacuo. Dissolve the residue in ethyl acetate (100 mL), wash with water (2×20 mL) and brine (20 mL), dry (Na2SO4) the organic phase, filter and concentrate to afford an oil. Purify the oil by flash chromatography (silica gel, 7×15 cm, ethyl acetate) to afford 0.97 g of 4-(1-vinyl-1H-benzoimidazol-2-yl)-[1,4]diazepane-1-carboxylic acid tert-butyl ester as an oil, Rf=0.52 (silica gel, ethyl acetate).

Workup

  1. temperatureheat at 50° C. for four hours
  2. stirringstir at room temperature for two hours
  3. temperatureCool to 0° C.
  4. customquench by addition of saturated ammonium chloride solution (5 mL)
  5. concentrationconcentrate in vacuo
  6. dissolutionDissolve the residue in ethyl acetate (100 mL)
  7. washwash with water (2×20 mL) and brine (20 mL)
  8. dry with materialdry (Na2SO4) the organic phase
  9. filtrationfilter
  10. concentrationconcentrate
  11. customto afford an oil
  12. customPurify the oil by flash chromatography (silica gel, 7×15 cm, ethyl acetate)

Sources & evidence

ORD record
ord-39c81b06047d4120b6980ba1973bd9e4
Source dataset
uspto-grants-2002_07
Patent number
US06423704B1

Reaction notes

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