Sodium hydride → 2-[3-(tert-Butoxycarbonyl-phenethyl-amino)-propylsulfanyl]-benzoimidazole

HRID 2389487Notes

Reaction equation

HRID 2389487 reaction equation
[C:1]([O:5][C:6](=[O:16])[NH:7][CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Cl[CH2:20][CH2:21][CH2:22]I.[NH:24]1[C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=2[N:26]=[C:25]1[S-:33].[Na+]>CN(C=O)C>[C:1]([O:5][C:6]([N:7]([CH2:8][CH2:9][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)[CH2:20][CH2:21][CH2:22][S:33][C:25]1[NH:24][C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=2[N:26]=1)=[O:16])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 813631-Chloro-3-iodopropaneHCID 3541750tert-butyl N-(2-phenylethyl)carbamateHCID 23699095sodium 1H-benzoimidazole-2-thiolate

Product 1

HCID 693165952-[3-(tert-Butoxycarbonyl-phenethyl-amino)-propylsulfanyl]-benzoimidazoleYield 14%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Phenethyl-carbamic acid tert-butyl ester (1107 mg, 5.0 mmol) is dissolved in dry DMF (7.75 ml). To this solution, sodium hydride (60% w/w in oil, 302 mg, 7.55 mmol) is added under vigorous stirring and stirring is continued for 30 min. Then 1-chloro-3-iodo-propane (250 mg, 5.0 mmol) is dropped into the solution followed by stirring for 2 h at rt and another hour at 50° C. After switching off the heating and addition of sodium 1H-benzoimidazole-2-thiolate (1722 mg, 10 mmol) the mixture is allowed to stir overnight at rt. All the DMF is evaporated in vacuo and the remaining crude is dissolved in DCE. This organic phase is washed twice with water, dried over Na2SO4 and evaporated to give the crude product which is purified by flash chromatography on silica gel (AcOEt/heptane, 1:9 to 1:1), yielding the title compound (289 mg) in 14% as a colourless oil: tR=2.24 min (LC-2), ESI-MS (pos.): m/z 412.43 [M+H]+, MS (neg.): m/z 410.46 [M−H]+; 1H-NMR (CDCl3): δ (ppm) 1.48 (s, 9H, tBu), 1.89 (br. s, 2H, SCH2CH2), 2.83 (t, 2H, PhCH2CH2N), 3.09 (br. s, 2H), 3.26 (br. s, 1H), 3.42 (t, 2H, PhCH2CH2N), 3.47 (br. s, 2H), 7.13-7.30 (m, 7Harom), 7.52 (m, 2H).

Workup

  1. stirringstirring
  2. stirringby stirring for 2 h at rt and another hour at 50° C
  3. stirringto stir overnight at rt
  4. customAll the DMF is evaporated in vacuo
  5. dissolutionthe remaining crude is dissolved in DCE
  6. washThis organic phase is washed twice with water
  7. dry with materialdried over Na2SO4
  8. customevaporated
  9. customto give the crude product which
  10. customis purified by flash chromatography on silica gel (AcOEt/heptane, 1:9 to 1:1)

Sources & evidence

ORD record
ord-81f2f2fa9ad64fafad0b2cc7eac02b2f
Source dataset
uspto-grants-2012_09
Patent number
US08273740B2

Reaction notes

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