Ethyl chloroformate → carbonic acid 9-benzhydryloxy-7-[2-(4-fluoro-phenyl)-ethyl]-6,8-dioxo-7,8-dihydro-6H-pyrrolo[3,4-g]quinolin-5-yl ester ethyl ester

HRID 853707Notes

Reaction equation

HRID 853707 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][N:10]2[C:22](=[O:23])[C:21]3[C:20]([OH:24])=[C:19]4[C:14]([CH:15]=[CH:16][CH:17]=[N:18]4)=[C:13]([OH:25])[C:12]=3[C:11]2=[O:26])=[CH:4][CH:3]=1.[OH-].[Na+].[CH2:29]([O:31][C:32](Cl)=[O:33])[CH3:30].[C:35]1([CH:41]([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[N+]#N)[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>O1CCOCC1.ClCCl.O>[CH2:29]([O:31][C:32](=[O:33])[O:25][C:13]1[C:12]2[C:11](=[O:26])[N:10]([CH2:9][CH2:8][C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)[C:22](=[O:23])[C:21]=2[C:20]([O:24][CH:41]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)=[C:19]2[C:14]=1[CH:15]=[CH:16][CH:17]=[N:18]2)[CH3:30]

Participants

8

Reactant 4

HCID 10928Ethyl chloroformateHCID 14798Sodium HydroxideHCID 58928810Diphenyl-methanediazoniumHCID 178515143HCID 178515143, compound

Product 1

HCID 58928851carbonic acid 9-benzhydryloxy-7-[2-(4-fluoro-phenyl)-ethyl]-6,8-dioxo-7,8-dihydro-6H-pyrrolo[3,4-g]quinolin-5-yl ester ethyl esterYield 65%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
0 °C

Procedure

7-[2-(4-Fluoro-phenyl)-ethyl]-5,9-dihydroxy-pyrrolo[3,4-g]quinoline-6,8-dione 310 (250 mg, 0.71 mmol).was dissolved in dioxane (3.6 ml) and H2O (2.4 ml) and cooled to 0° C. After 1.0 M NaOH (1.42 ml, 1.42 mmol) and ethylchloroformate (84.6 mg, 0.78 mmol) were added, the reaction was stirred at 0° C. for one hour. The reaction mixture was quenched with the addition of acetic acid (0.6 ml) and concentrated in vacuo. The crude mixture was diluted with ethyl acetate and washed once with 5% Citric Acid (aqueous), twice with water, once with brine, dried over magnesium sulfate, and concentrated in vacuo. The resulting residue was dissolved in 1,2-dichloroethane (4.0 ml) and to this was added diphenyl-methanediazonium 38 (252 mg, 1.3 mmol). The reaction mixture was then stirred overnight at room temperature. Following dilution with dichloromethane, the reaction mixture was washed with once with water, once with brine, dried over magnesium sulfate, and concentrated in vacuo. The residue was then purified by silica gel chromatography (1/1—hexane/ethyl acetate) to afford carbonic acid 9-benzhydryloxy-7-[2-(4-fluoro-phenyl)-ethyl]-6,8-dioxo-7,8-dihydro-6H-pyrrolo[3,4-g]quinolin-5-yl ester ethyl ester 311 (251 mg, 0.425 mmol, 65%). 1H NMR (d-DMSO) δ 9.19 (dd, 1H), 8.52 (dd, 1H), 7.90 (s, 1H), 7.80 (m, 1H), 7.54 (m, 4H), 7.20 (m, 8H), 7.02 (t, 2H), 4.24 (q, 2H), 3.79 (t, 2H), 2.90 (t, 2H), 1.25 (t, 3H). MS: 599.2 (M+23).

Workup

  1. customThe reaction mixture was quenched with the addition of acetic acid (0.6 ml)
  2. concentrationconcentrated in vacuo
  3. additionThe crude mixture was diluted with ethyl acetate
  4. washwashed once with 5% Citric Acid (aqueous), twice with water, once with brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. dissolutionThe resulting residue was dissolved in 1,2-dichloroethane (4.0 ml)
  8. stirringThe reaction mixture was then stirred overnight at room temperature
  9. washthe reaction mixture was washed with once with water
  10. dry with materialonce with brine, dried over magnesium sulfate
  11. concentrationconcentrated in vacuo
  12. customThe residue was then purified by silica gel chromatography (1/1—hexane/ethyl acetate)

Sources & evidence

ORD record
ord-7f5d260eea07414e80ea691aba245b1f
Source dataset
uspto-grants-2007_08
Patent number
US07253180B2

Reaction notes

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