Sodium hydride → HCID 43438759, compound

HRID 1471424Notes

Reaction equation

HRID 1471424 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]([OH:12])=[O:11])=[CH:2]1.[H-].[Na+].[Br:15][C:16]1[CH:23]=[CH:22][C:19]([CH2:20]Br)=[C:18]([F:24])[CH:17]=1>CN(C=O)C>[Br:15][C:16]1[CH:23]=[CH:22][C:19]([CH2:20][N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[C:3]([C:10]([OH:12])=[O:11])=[CH:2]2)=[C:18]([F:24])[CH:17]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 69867Indole-3-Carboxylic AcidHCID 27336604-Bromo-2-fluorobenzyl bromide

Product 1

HCID 43438759HCID 43438759, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

In an oven dried 20 mL scintillation vial, indole-3-carboxylic acid (500 mg, 3.10 mmol) was massed. The vial was charged with a stir bar and DMF (10 mL), and then capped under an atmosphere of nitrogen. The solution was cooled to 0° C., followed by addition of NaH (60% dispersion in mineral oil, 375 mg, 9.38 mmol). The reaction was allowed to stir for 5 min. 4-Bromo-2-fluorobenzyl bromide (1.00 g, 3.73 mmol) was added in one portion, and the reaction was allowed to stir 15 min at 0° C. then warmed to 25° C. over 30 min. Reaction was monitored by LCMS, and upon completion was quenched cautiously with H2O. The reaction mixture was diluted with dichloromethane (20 mL) and the organic layer was acidified to pH 1 with 1M HCl. The aqueous layer was extracted with dichloromethane (3×20 mL). The organic layers were combined, dried over MgSO4, filtered, and concentrated in vacuo. The crude material was purified by silica gel chromatography eluting with hexanes/ethyl acetate (0 to 100%) to afford 1-(4-bromo-2-fluorobenzyl)-1H-indole-3-carboxylic acid as a solid (LCMS: RT=0.795 min, (M+H)+ m/z=348).

Workup

  1. additionThe vial was charged with a stir bar
  2. stirringto stir 15 min at 0° C.
  3. temperaturethen warmed to 25° C. over 30 min
  4. customReaction
  5. customupon completion was quenched cautiously with H2O
  6. additionThe reaction mixture was diluted with dichloromethane (20 mL)
  7. extractionThe aqueous layer was extracted with dichloromethane (3×20 mL)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude material was purified by silica gel chromatography
  12. washeluting with hexanes/ethyl acetate (0 to 100%)

Sources & evidence

ORD record
ord-e4adf2bc85fd48b8a5580923a432432a
Source dataset
uspto-grants-2015_04
Patent number
US09012445B2

Reaction notes

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