Sodium hydride → 5-Methoxy-9-(4-methoxy-benzyloxy)-7-(4-trifluoromethyl-benzyl)-6,7-dihydro-pyrrolo[3,4-g]quinolin-8-one

HRID 853702Notes

Reaction equation

HRID 853702 reaction equation
[CH3:1][O:2][C:3]1[C:12]2[CH2:13][NH:14][C:15](=[O:16])[C:11]=2[C:10]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)=[C:9]2[C:4]=1[CH:5]=[CH:6][CH:7]=[N:8]2.[H-].[Na+].[F:29][C:30]([F:40])([F:39])[C:31]1[CH:38]=[CH:37][C:34]([CH2:35]Br)=[CH:33][CH:32]=1>CN(C)C=O>[CH3:1][O:2][C:3]1[C:12]2[CH2:13][N:14]([CH2:35][C:34]3[CH:33]=[CH:32][C:31]([C:30]([F:29])([F:39])[F:40])=[CH:38][CH:37]=3)[C:15](=[O:16])[C:11]=2[C:10]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)=[C:9]2[C:4]=1[CH:5]=[CH:6][CH:7]=[N:8]2

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1230621-(Bromomethyl)-4-(trifluoromethyl)benzeneHCID 589287845-Methoxy-9-(4-methoxy-benzyloxy)-6,7-dihydro-pyrrolo[3,4-g]quinolin-8-one

Product 1

HCID 589289465-Methoxy-9-(4-methoxy-benzyloxy)-7-(4-trifluoromethyl-benzyl)-6,7-dihydro-pyrrolo[3,4-g]quinolin-8-oneYield 35.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

5-Methoxy-9-(4-methoxy-benzyloxy)-6,7-dihydro-pyrrolo[3,4-g]quinolin-8-one 304 (25.4 mg, 0.073 mmol,) was dissolved in dimethylformamide (0.4 ml) and cooled to 0° C. Sodium hydride (3.6 mg, 0.095 mmol) was added, followed by stirring at 0° C. for 5 minutes. 4-trifluoromethyl-benzylbromide (21.0 mg, 0.088 mmol) was added and the reaction mixture was allowed to warm to room temperature and kept at room temperature with stirring for 5 minutes. It was cooled to 0° C., quenched with acetic acid (0.030 ml), and concentrated in vacuo. The mixture was diluted with ethyl acetate, washed twice with water, once with brine, dried over magnesium sulfate, and concentrate in vacuo. The residue was purified by silica gel chromatography (99/1—ethyl acetate/acetic acid) to afford 5-Methoxy-9-(4-methoxy-benzyloxy)-7-(4-trifluoromethyl-benzyl)-6,7-dihydro-pyrrolo[3,4-g]quinolin-8-one 305 (13 mg, 0.026 mmol, 35%). 1H NMR δ 9.15 (dd, 1H), 8.60 (dd, 1H), 7.60 (m, 4H), 7.40 (d, 2H), 6.80 (d, 2H), 5.85 (s, 2H), 4.80 (s, 2H), 4.42 (s, 2H), 3.98 (s, 3H), 3.86 (s, 3H). MS: 509.2 (M+1).

Workup

  1. temperatureto warm to room temperature
  2. customkept at room temperature
  3. stirringwith stirring for 5 minutes
  4. temperatureIt was cooled to 0° C.
  5. customquenched with acetic acid (0.030 ml)
  6. concentrationconcentrated in vacuo
  7. additionThe mixture was diluted with ethyl acetate
  8. washwashed twice with water, once with brine
  9. dry with materialdried over magnesium sulfate
  10. concentrationconcentrate in vacuo
  11. customThe residue was purified by silica gel chromatography (99/1—ethyl acetate/acetic acid)

Sources & evidence

ORD record
ord-54907bb03184466aa5fdde6543333549
Source dataset
uspto-grants-2007_08
Patent number
US07253180B2

Reaction notes

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