Dimethyl oxalate → (1-methyl-4-methoxyl-1H-indol-7-yl)-oxo-acetic acid methyl ester

HRID 2215794Notes

Reaction equation

HRID 2215794 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[C:6]([O:12][CH3:13])[CH:7]=[CH:8][C:9]=2Br)[CH:4]=[CH:3]1.C([Li])(C)(C)C.[C:19](OC)(=[O:24])[C:20]([O:22][CH3:23])=[O:21]>C1COCC1>[CH3:23][O:22][C:20](=[O:21])[C:19]([C:9]1[CH:8]=[CH:7][C:6]([O:12][CH3:13])=[C:5]2[C:10]=1[N:2]([CH3:1])[CH:3]=[CH:4]2)=[O:24]

Participants

5

Reactant 3

HCID 11120Dimethyl oxalateHCID 219499811-Methyl-4-methoxyl-7-bromoindoleHCID 178418306HCID 178418306, compound

Product 1

HCID 21055226(1-methyl-4-methoxyl-1H-indol-7-yl)-oxo-acetic acid methyl esterYield 58.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1-methyl-4-methoxyl-7-bromoindole (1.17 g, 4.87 mmol) in THF (33 mL) was cooled to −78° C. and a solution of tert-butyl lithium in pentanes (1.7 M, 6.3 mL, 10.7 mmol) added dropwise over 30 min. After 30 min at −78° C., the mixture was treated with dimethyl oxalate (1.44 g, 12.2 mmol) in one portion. After 15 min, the mixture was allowed to warm to room temperature and stirred 4 h. The reaction mixture was quenched with water and extracted with ethyl acetate. The extract was washed with brine and dried (Na2SO4), and concentrated. Flash chromatography (EtOAc/hexanes) afforded the title compound (0.7 g, 58.1%). 1H NMR (400 MHz, CDCl3) 3.95 (s, 3H), 4.0 (s, 3 H), 4.02 (s, 3H), 6.56 (d, J=8.61 Hz, 1H), 6.67 (d, J=3.13 Hz, 1H), 6.99 (d, J=3.13 Hz, 1H), 7.61 (d, j=8.6 Hz, 1H); MS (ES, m/z): C13H13NO4: 248.16 (M++1).

Workup

  1. waitAfter 15 min
  2. customThe reaction mixture was quenched with water
  3. extractionextracted with ethyl acetate
  4. washThe extract was washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-ae3273dc57e647acb24632519716f25a
Source dataset
uspto-grants-2006_09
Patent number
US07109229B2

Reaction notes

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