Cornforth reagent → (1-Methyl-1H-imidazol-2-yl)(4-(tetrahydro-2H-pyran-2-yloxy)phenyl)methanone
Reaction equation
[Cr](O[Cr]([O-])(=O)=O)([O-])(=O)=O.[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1.[CH3:22][N:23]1[CH:27]=[CH:26][N:25]=[C:24]1[CH:28]([C:30]1[CH:35]=[CH:34][C:33]([O:36][CH:37]2[CH2:42][CH2:41][CH2:40][CH2:39][O:38]2)=[CH:32][CH:31]=1)[OH:29]>C(Cl)Cl>[CH3:22][N:23]1[CH:27]=[CH:26][N:25]=[C:24]1[C:28]([C:30]1[CH:31]=[CH:32][C:33]([O:36][CH:37]2[CH2:42][CH2:41][CH2:40][CH2:39][O:38]2)=[CH:34][CH:35]=1)=[O:29]Participants
Conditions
- Temperature
- 0 °C
Procedure
Pyridinium dichromate (36 g, 95.7 mmol) was added to a solution of 9.1 (21 g, 72.7 mmol) in DCM (100 mL) at 0° C. in several portions. The mixture was stirred at 0° C. for 1 hour and at room temperature for 6 hours. Silica gel (75 g) was added to the reaction mixture, and the resulting slurry was filtered through a pad of silica gel. The solid was washed with DCM (200 mL). The filtrate was washed with water and saturated brine, dried over Na2SO4, filtered and concentrated under reduced pressure to give an oily residue, which was flash chromatographed (silica gel, 0-30% EtOAc in hexane) to afford ketone 9.2 as yellow solid (16 g). 1H NMR (500 MHz) (CDCl3) δ 8.33-8.35 (m, 2H); 7.10-7.29 (m, 4H); 5.56 (t, J=3.0 Hz, 1H); 4.08 (s, 3H); 3.85-3.90 (m, 1H); 3.61-3.65 (m, 1H); 2.03 (m, 1H); 1.90-1.91 (m, 2H); 1.69-1.74 (m, 2H); 1.61-1.64 (m, 1H).
Workup
- additionSilica gel (75 g) was added to the reaction mixture
- filtrationthe resulting slurry was filtered through a pad of silica gel
- washThe solid was washed with DCM (200 mL)
- washThe filtrate was washed with water and saturated brine
- dry with materialdried over Na2SO4
- filtrationfiltered
- concentrationconcentrated under reduced pressure
- customto give an oily residue, which
- customchromatographed (silica gel, 0-30% EtOAc in hexane)
Sources & evidence
- ORD record
- ord-b3b8768fac2b468887f54248af980312
- Source dataset
- uspto-grants-2008_12
- Patent number
- US07465804B2
Reaction notes
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