Sodium hydride → 1-[2-(1-benzyl-pyrrolidin-3-yl)-ethyl]-5-fluoro-1H-indole

HRID 2298245Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.[H-].[Na+].[CH3:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19].C(O[CH2:24][CH3:25])(=O)C.CO>CN(C=O)C.C(OCC)(=O)C>[CH2:13]([N:7]1[CH2:8][CH2:4][CH:24]([CH2:25][N:7]2[C:8]3[C:4](=[CH:3][C:2]([F:1])=[CH:10][CH:9]=3)[CH:5]=[CH:6]2)[CH2:5][CH2:6]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[CH2:13]([N:7]1[CH2:8][CH2:4][CH:5]([CH2:24][CH2:25][N:7]2[C:8]3[C:4](=[CH:3][C:2]([F:1])=[CH:10][CH:9]=3)[CH:5]=[CH:6]2)[CH2:6]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

Conditions

Temperature: 50 °C

Procedure

5-Fluoro-indole (391 mg, 2.89 mmol) in DMF (2 mL) was added drop-wise to a stirred suspension of sodium hydride (60%, 116 mg, 3.04 mmole) in DMF (2 mL) at 0° C. After 30 minutes compound a) (987 mg, 3.47 mmol), dissolved in DMF (6 mL), was added and the reaction mixture was stirred at 50° C. over night. The mixture was diluted with ethyl acetate, washed three times with water and dried over sodium sulfate. Evaporation of the solvent gave the crude product as a mixture of two constitution isomers. Silica gel chromatography (heptane-ethyl acetate-methanol, 20:80:5) gave the sub-title compound (138 mg, 15%) and 1-[2-(1-benzyl-pyrrolidin-3-yl)-ethyl]-5-fluoro-1H-indole (338 mg 36%).

Workup

additionwas added
washwashed three times with water
dry with materialdried over sodium sulfate
customEvaporation of the solvent
customgave the crude product
additionas a mixture of two constitution isomers

Sources & evidence

ORD record: ord-769dde9bec29457b84d5ab5ef880d6f6
Source dataset: uspto-grants-2002_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06492406B1

Reaction notes

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