Ammonium Chloride → HCID 22285062, compound

HRID 1061892Notes

Reaction equation

HRID 1061892 reaction equation
[CH3:1][N:2]1[CH2:10][C:9]2[C:8]3[CH:11]=[CH:12][C:13]([C:15]([C:17]4[N:18]=[CH:19][N:20]([C:22]([C:35]5[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=5)([C:29]5[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=5)[C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=5)[CH:21]=4)=[O:16])=[CH:14][C:7]=3[CH:6]=[CH:5][C:4]=2[C:3]1=[O:41].[CH3:42][Mg]Br.[Cl-].[NH4+]>C1COCC1>[OH:16][C:15]([C:13]1[CH:12]=[CH:11][C:8]2[C:9]3[CH2:10][N:2]([CH3:1])[C:3](=[O:41])[C:4]=3[CH:5]=[CH:6][C:7]=2[CH:14]=1)([C:17]1[N:18]=[CH:19][N:20]([C:22]([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH:21]=1)[CH3:42]

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 22285042HCID 22285042, compoundHCID 178418573HCID 178418573, compound2×

Product 1

HCID 22285062HCID 22285062, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

2-Methyl-7-[(1-trityl-1H-imidazol-4-yl)carbonyl]-1,2-dihydro-3H-benzo[e]isoindol-3-one (1.07 g) was dissolved in THF (22 mL) and cooled to 0° C., and then a solution (1.0 M: 3.0 mL) of methylmagnesium bromide in THF was added dropwise. The reaction mixture was stirred at room temperature for 1 hr. and a solution (1.0 M: 3.0 mL) of methylmagnesium bromide in THF was added. The mixture was further stirred at room temperature for 30 min., and 20% aqueous ammonium chloride solution 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: dichloromethane-methanol=100:1→40:1) to give 7-(1-hydroxy-1-(1-trityl-1H-imidazol-4-yl)ethyl]-2-methyl-1,2-dihydro-3H-benzo[e]isoindol-3-one (1.00 g) as an amorphous solid. This amorphous solid was dissolved in 90% formic acid (9 mL) and THF (9 mL) and the solution was stirred with heating at 60° C. for 2 hrs. The reaction mixture was concentrated and the residue was neutralized with saturated aqueous sodium hydrogen carbonate. Sodium chloride was added and the mixture was extracted three times with a mixed solution of ethyl acetate-THF (1:1) under salting out. The combined extracted layer was dried over anhydrous magnesium sulfate and concentrated. The residue was suspended in ethyl acetate, filtrated and recrystallized from ethanol-water to give the title compound (0.20 g) as pale-brown crystals.

Workup

  1. stirringThe mixture was further stirred at room temperature for 30 min.
  2. customthe reaction
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with ethyl acetate
  5. washThe combined organic layers were washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography (carrier: silica gel, developing solvent: dichloromethane-methanol=100:1→40:1)

Sources & evidence

ORD record
ord-0ac05ced9dac43f9a412de2af9847d58
Source dataset
uspto-grants-2005_11
Patent number
US06960586B2

Reaction notes

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