1-Methylimidazole → HCID 69020312, compound

HRID 860804Notes

Reaction equation

HRID 860804 reaction equation
[Li]CCCC.[CH3:6][N:7]1[CH:11]=[CH:10][N:9]=[CH:8]1.Cl[Si](CC)(CC)CC.[Cl:20][C:21]1[CH:48]=[CH:47][C:24]([C:25]([C:27]2[CH:28]=[CH:29][C:30]3[N:36]([CH3:37])[C:35](=[O:38])[CH2:34][NH:33][CH:32]([C:39]4[CH:44]=[CH:43][CH:42]=[C:41]([Cl:45])[CH:40]=4)[C:31]=3[CH:46]=2)=[O:26])=[CH:23][CH:22]=1>CCCCCC.C1COCC1>[Cl:45][C:41]1[CH:40]=[C:39]([CH:32]2[C:31]3[CH:46]=[C:27]([C:25]([C:24]4[CH:47]=[CH:48][C:21]([Cl:20])=[CH:22][CH:23]=4)([OH:26])[C:11]4[N:7]([CH3:6])[CH:8]=[N:9][CH:10]=4)[CH:28]=[CH:29][C:30]=3[N:36]([CH3:37])[C:35](=[O:38])[CH2:34][NH:33]2)[CH:44]=[CH:43][CH:42]=1

Participants

7

Reactant 4

HCID 13901-MethylimidazoleHCID 13819ChlorotriethylsilaneHCID 69021420HCID 69021420, compoundHCID 178418339Butyllithium2×

Product 1

HCID 69020312HCID 69020312, compoundYield 8.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent2×

Conditions

Temperature
-70 °C

Procedure

BuLi 1.6M in hexane (27.4 ml) was added dropwise at −70° C. under N2 flow to a mixture of 1-methyl-1H-imidazole (0.0439 mol) in THF (140 ml). The mixture was stirred for 30 min. ClSiEt3 (0.0439 mol) was added. The mixture was brought slowly to room temperature and cooled again to −70° C. BuLi 1.6M in hexane (27.4 ml) was added dropwise. The mixture was stirred for 1 hour, brought quickly to −15° C. and cooled to −70° C. A solution of intermediate (8) (0.02 mol) in THF (90 ml) was added dropwise. The mixture was stirred at −50° C. for 30 min, then hydrolyzed and extracted with EtOAc. The organic layer was separated, dried (MgSO4), filtered and the solvent was evaporated till dryness. The residue (17.5 g) was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 94/6/0.1 and 93/7/0.1; 20–45 μm). The pure fractions were collected and the solvent was evaporated. The residue was crystallized from CH3CN, EtOAc and 2-propanone. The precipitate was filtered off and dried, yielding 0.8 g (8.5%) of 5-(3-chlorophenyl)-7-[(4-chlorophenyl)hydroxy(1-methyl-1H-imidazol-5-yl)methyl]-1,3,4,5-tetrahydro-1-methyl-2H-1,4-benzodiazepin-2-one, mp. 208° C.

Workup

  1. customwas brought slowly to room temperature
  2. stirringThe mixture was stirred for 1 hour
  3. custombrought quickly to −15° C.
  4. temperaturecooled to −70° C
  5. stirringThe mixture was stirred at −50° C. for 30 min
  6. extractionhydrolyzed and extracted with EtOAc
  7. customThe organic layer was separated
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. customthe solvent was evaporated till dryness
  11. customThe residue (17.5 g) was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 94/6/0.1 and 93/7/0.1; 20–45 μm)
  12. customThe pure fractions were collected
  13. customthe solvent was evaporated
  14. customThe residue was crystallized from CH3CN, EtOAc and 2-propanone
  15. filtrationThe precipitate was filtered off
  16. customdried

Sources & evidence

ORD record
ord-2cb3066d3aa341cfacaf08ad2a4afe50
Source dataset
uspto-grants-2006_12
Patent number
US07153958B2

Reaction notes

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