Sodium Bicarbonate → (RS)-2-{2-[4-((5-fluoro-3-indolyl)methyl)piperidino]ethyl}-3-methoxyisoindolinone

HRID 1196612Notes

Reaction equation

Br[CH2:2][CH2:3][N:4]1[CH:12]([O:13][CH3:14])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]1=[O:15].[F:16][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[NH:22][CH:21]=[C:20]2[CH2:26][CH:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1.C(=O)(O)[O-].[Na+]>CN(C)C=O.O1CCCC1>[F:16][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[NH:22][CH:21]=[C:20]2[CH2:26][CH:27]1[CH2:32][CH2:31][N:30]([CH2:2][CH2:3][N:4]2[CH:12]([O:13][CH3:14])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]2=[O:15])[CH2:29][CH2:28]1

Participants

Conditions

Temperature: 20 °C

Procedure

The procedure is as in Example 25, starting with (RS)-2-(2-bromoethyl)-3-methoxyisoindolinone (2.4 g), 4-[(5-fluoro-3-indolyl)methyl]piperidine (2.1 g) and sodium bicarbonate (0.74 g) in a mixture of dimethylformamide (50 cc) and tetrahydrofuran (40 cc). The mixture is heated to boiling for 10 hours and then cooled to a temperature in the region of 20° C. After purification by flash chromatography on a silica column under a stream of nitrogen at moderate pressure (0.5-1.5 bar) with ethyl acetate as eluent, and recrystallization a first time in acetonitrile (40 cc) and then in methyl ethyl ketone (35 cc), (RS)-2-{2-[4-((5-fluoro-3-indolyl)methyl)piperidino]ethyl}-3-methoxyisoindolinone (0.8 g), m.p. 175° C., is obtained.

Workup

temperatureThe mixture is heated
customAfter purification by flash chromatography on a silica column under a stream of nitrogen at moderate pressure (0.5-1.5 bar) with ethyl acetate as eluent
customrecrystallization a first time in acetonitrile (40 cc)

Sources & evidence

ORD record: ord-f629536935c244ae81c0a5c5b64b1dd5
Source dataset: uspto-grants-1992_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05114949

Reaction notes

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