Sodium hydride → [6-Chloro-3-(2,2,2-trifluoro-acetyl)-indol-1-yl]-acetic acid methyl ester

HRID 505074Notes

Reaction equation

HRID 505074 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])=[CH:7][NH:8]2)=[CH:4][CH:3]=1.[H-].[Na+].[CH3:19][O:20][C:21](=[O:24])[CH2:22]Br>CN(C=O)C>[CH3:19][O:20][C:21](=[O:24])[CH2:22][N:8]1[C:9]2[C:5](=[CH:4][CH:3]=[C:2]([Cl:1])[CH:10]=2)[C:6]([C:11](=[O:16])[C:12]([F:13])([F:14])[F:15])=[CH:7]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 60984Methyl bromoacetateHCID 224972521-(6-Chloro-3-indolyl)-2,2,2-trifluoroethanone

Product 1

HCID 66743651[6-Chloro-3-(2,2,2-trifluoro-acetyl)-indol-1-yl]-acetic acid methyl esterYield 81.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 6.65 g (0.0265 mol, 1 eq.) of 1-(6-chloro-1H-indol-3-yl)-2,2,2-trifluoro-ethanone in 25 ml of DMF at 0° C. were added 1.23 g of NaH (55% in oil, 0.0282 mol, 1.05 eq). After 30 minutes, 4.31 g (0.0282 mol, 1.05 eq.) of bromo-acetic acid methyl ester were added and the temperature raised to RT, and stirring was continued overnight. The reaction was quenched by the addition of aq.HCl 0.1 M, and the product was extracted with EtOAc and the combined organic phases dried over Na2SO4. Recrystallisation in Et2O/Heptane afforded 6.90 g (80%) of [6-chloro-3-(2,2,2-trifluoro-acetyl)-indol-1-yl]-acetic acid methyl ester as white crystals.

Workup

  1. waitwas continued overnight
  2. customThe reaction was quenched by the addition of aq
  3. extractionHCl 0.1 M, and the product was extracted with EtOAc
  4. dry with materialthe combined organic phases dried over Na2SO4
  5. customRecrystallisation in Et2O/Heptane

Sources & evidence

ORD record
ord-bb2bfdee91584ad3bd7a89048641d556
Source dataset
uspto-grants-2010_08
Patent number
US07781436B2

Reaction notes

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