Ammonium Chloride → 7-[1-hydroxy-2-methyl-1-(1-trityl-1H-imidazol-4-yl)propyl]-2-methyl-1,2-dihydro-3H-benzo[e]isoindol-3-one

HRID 1061894Notes

Reaction equation

HRID 1061894 reaction equation
Br[C:2]1[CH:16]=[CH:15][C:5]2[C:6]3[CH2:7][N:8]([CH3:14])[C:9](=[O:13])[C:10]=3[CH:11]=[CH:12][C:4]=2[CH:3]=1.C([Li])CCC.[CH3:22][CH:23]([CH3:50])[C:24]([C:26]1[N:27]=[CH:28][N:29]([C:31]([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH:30]=1)=[O:25].[Cl-].[NH4+]>C1COCC1.CCCCCC>[OH:25][C:24]([C:2]1[CH:16]=[CH:15][C:5]2[C:6]3[CH2:7][N:8]([CH3:14])[C:9](=[O:13])[C:10]=3[CH:11]=[CH:12][C:4]=2[CH:3]=1)([C:26]1[N:27]=[CH:28][N:29]([C:31]([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)([C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH:30]=1)[CH:23]([CH3:50])[CH3:22]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 10150490isopropyl(1-trityl-1H-imidazol-4-yl)ketoneHCID 222850567-bromo-2-methyl-1,2-dihydro-3H-benzo[e]isoindol-3-oneHCID 178418339Butyllithium

Product 1

HCID 101670197-[1-hydroxy-2-methyl-1-(1-trityl-1H-imidazol-4-yl)propyl]-2-methyl-1,2-dihydro-3H-benzo[e]isoindol-3-oneYield 53.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-70 °C

Procedure

7-Bromo-2-methyl-1,2-dihydro-3H-benzo[e]isoindol-3-one (0.14 g) was suspended in THF (6 mL) and dissolved by heating. This solution was cooled to −70° C. and a solution (1.6 M: 0.75 mL) of n-butyllithium in hexane was slowly added dropwise. After stirring for 1 hr., a solution (1 mL) of 2-methyl-1-(1-trityl-1H-imidazol-4-yl)-1-propanone (0.16 g) in THF was added dropwise. After stirring at −70° C. for 30 min., 20% aqueous ammonium chloride was added to stop the reaction. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by column chromatography (carrier: silica gel, developing solvent: hexane-ethyl acetate, 1:1—ethyl acetate) to give the title compound (0.13 g) as colorless crystals.

Workup

  1. dissolutiondissolved
  2. temperatureby heating
  3. stirringAfter stirring at −70° C. for 30 min.
  4. customthe reaction
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted with ethyl acetate
  7. washThe combined organic layers were washed with saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated
  10. customThe residue was purified by column chromatography (carrier: silica gel, developing solvent: hexane-ethyl acetate, 1:1—ethyl acetate)

Sources & evidence

ORD record
ord-6323ab8ae8d141fc9fa9ee3459ae25a5
Source dataset
uspto-grants-2005_11
Patent number
US06960586B2

Reaction notes

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