Methyl iodide → tert-butyl (4-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazol-5-yl)methyl(methyl)carbamate

HRID 475261Notes

Reaction equation

HRID 475261 reaction equation
[Cl:1][C:2]1[C:10]2[N:9]=[CH:8][N:7]([CH:11]3[CH2:16][CH2:15][CH2:14][CH2:13][O:12]3)[C:6]=2[CH:5]=[CH:4][C:3]=1[CH2:17][NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22].[H-].[Na+].I[CH3:29]>CN(C=O)C>[Cl:1][C:2]1[C:10]2[N:9]=[CH:8][N:7]([CH:11]3[CH2:16][CH2:15][CH2:14][CH2:13][O:12]3)[C:6]=2[CH:5]=[CH:4][C:3]=1[CH2:17][N:18]([CH3:29])[C:19](=[O:25])[O:20][C:21]([CH3:22])([CH3:24])[CH3:23]

Participants

5

Reactant 3

HCID 6328Methyl iodide2×HCID 24758Sodium hydride2×HCID 86694746tert-butyl (4-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazol-5-yl)methylcarbamate

Product 1

HCID 86694745tert-butyl (4-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazol-5-yl)methyl(methyl)carbamateYield 56.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 216 (620 mg, 1.7 mmol) in DMF (8 mL) at 0° C. was added NaH (102 mg, 2.54 mmol, 60% in oil). The reaction was warmed to RT and stirred for 25 min then re-cooled to 0° C. and iodomethane (0.19 mL, 3.05 mmol) was added. The reaction was warmed to RT and stirred for 3 h. The conversion was low so the reaction mixture was cooled back to 0° C. and additional NaH (67 mg, 1.69 mmol, 60% in oil) was added. The reaction was warmed to RT and stirred for 20 min, re-cooled to 0° C. and iodomethane (0.11 mL, 1.69 mmol) was added. The reaction was warmed to RT and stirred for 3 h then partitioned between EtOAc and H2O. The combined organic extracts were thrice washed with H2O, dried (Na2SO4), filtered and concentrated in vacuo. The crude residue was purified by SiO2 chromatography to afford 363 mg (56%) of tert-butyl (4-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazol-5-yl)methyl(methyl)carbamate (218): MS (ESI) m/z=380.2 [M+1]+.

Workup

  1. temperaturethen re-cooled to 0° C.
  2. temperatureThe reaction was warmed to RT
  3. stirringstirred for 3 h
  4. temperaturewas cooled back to 0° C.
  5. temperatureThe reaction was warmed to RT
  6. stirringstirred for 20 min
  7. temperaturere-cooled to 0° C.
  8. temperatureThe reaction was warmed to RT
  9. stirringstirred for 3 h
  10. customthen partitioned between EtOAc and H2O
  11. washwashed with H2O
  12. dry with materialdried (Na2SO4)
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customThe crude residue was purified by SiO2 chromatography

Sources & evidence

ORD record
ord-cf0028b7ff8648c39428446b8a7e1009
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Reaction notes

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