3-Chlorobenzaldehyde → 1-(3-chloro-phenyl)-2-(1-trityl-1H-imidazol-2-yl)-ethanol

HRID 2266776Notes

Reaction equation

HRID 2266776 reaction equation
CC(C)=O.C(=O)=O.[CH3:8][C:9]1[N:10]([C:14]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:11]=[CH:12][N:13]=1.CN(C)CCN(C)CCN(C)C.C([Li])CCC.[Cl:50][C:51]1[CH:52]=[C:53]([CH:56]=[CH:57][CH:58]=1)[CH:54]=[O:55]>O1CCCC1.C(OCC)(=O)C>[Cl:50][C:51]1[CH:52]=[C:53]([CH:54]([OH:55])[CH2:8][C:9]2[N:10]([C:14]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)[C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH:11]=[CH:12][N:13]=2)[CH:56]=[CH:57][CH:58]=1

Participants

8

Reactant 5

HCID 114773-ChlorobenzaldehydeHCID 18196PentamethyldiethylenetriamineHCID 6182462-Methyl-1-tritylimidazoleHCID 18522661Acetone cardiceHCID 178418339Butyllithium

Product 1

HCID 539134081-(3-chloro-phenyl)-2-(1-trityl-1H-imidazol-2-yl)-ethanolYield 72.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

To a stirred, cooled (−78° C., acetone/dry ice bath) solution of 2-methyl-1-tritylimidazole (1 g; CAS 23593-68-2) in tetrahydrofuran (THF) (15 ml) under an argon atmosphere was added pentamethyldiethylene-triamine (0.64 ml). n-butyllithium solution (2.0 ml; 1.6 M in hexanes) was then added dropwise over a period of 10 min. The reaction mixture soon turned to a dark red compact slurry. The mixture was then stirred at a temperature between −40° C. and −50° C. for 6 hours. After cooling again to −78° C., a solution of 3-chlorobenzaldehyde (0.86 g) in THF (5 ml) was added dropwise for 5 minutes. The mixture was stirred overnight, slowly warming up to room temperature. The clear yellow solution was diluted with ethyl acetate (30 ml) and washed with H2O. The aqueous phase was back extracted with ethyl acetate (EtOAc). The combined organics were washed with H2O and brine, dried over MgSO4, filtered and concentrated. The crude product was purified by column chromatography (silica gel; gradient CH2Cl2→CH2Cl2/methanol 92:8) to give 1-(3-chloro-phenyl)-2-(1-trityl-1H-imidazol-2-yl)-ethanol (1.04 g) as light yellow amorphous solid. MS (ISP): 243.3 ([Trt]+)

Workup

  1. stirringThe mixture was stirred overnight
  2. temperatureslowly warming up to room temperature
  3. washwashed with H2O
  4. extractionThe aqueous phase was back extracted with ethyl acetate (EtOAc)
  5. washThe combined organics were washed with H2O and brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by column chromatography (silica gel; gradient CH2Cl2→CH2Cl2/methanol 92:8)

Sources & evidence

ORD record
ord-677f9510ddb64b958eb94921e75ce804
Source dataset
uspto-grants-2010_12
Patent number
US07858653B2

Reaction notes

Loading…