Dimethyl oxalate → (1-methyl-5-methoxy-1H-indol-7-yl)-oxo-acetic acid methyl ester

HRID 2215784Notes

Reaction equation

HRID 2215784 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([O:12][CH3:13])=[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]=[C:7]([O:12][CH3:13])[CH:6]=[C:5]2[C:10]=1[N:2]([CH3:1])[CH:3]=[CH:4]2)=[O:24]

Participants

5

Reactant 3

HCID 11120Dimethyl oxalateHCID 219500181-Methyl-5-methoxy-7-bromoindoleHCID 178418306HCID 178418306, compound

Product 1

HCID 69642138(1-methyl-5-methoxy-1H-indol-7-yl)-oxo-acetic acid methyl esterYield 54.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1-methyl-5-methoxy-7-bromoindole (1.6 g, 6.66 mmol) in THF (44.5 mL) was cooled to −78° C. and a solution of tert-butyl lithium in pentanes (1.7 M, 8.62 mL, 14.7 mmol) added dropwise over 30 min. After 30 min at −78° C., the mixture was treated with dimethyl oxalate (1.96 g, 16.7 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, extracted with ethyl acetate, and the extracts washed with brine, dried (Na2SO4) and concentrated. Flash chromatography (EtOAc/hexanes) afforded the title compound (0.9 g, 54.7%) as bright yellow oil. 1HNMR (400 MHz, CDCl3) 3.83 (s, 3H), 3.87 (s, 3H), 4.00 (s, 3H), 6.51 (d, J=3.12 Hz, 1 H), 7.07 (d, J=3.13 Hz, 1H), 7.21 (d, J=2.35 Hz, 1H), 7.7.40 (d, J=2.34 Hz, 1H); MS (ES, m/z): C13H13NO4: 188.06 (M++1).

Workup

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

Sources & evidence

ORD record
ord-3f497061d07c4c6e928e7b4df9f547ac
Source dataset
uspto-grants-2006_09
Patent number
US07109229B2

Reaction notes

Loading…