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

HRID 2215781Notes

Reaction equation

HRID 2215781 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([CH3:12])=[CH:8][C:9]=2Br)[CH:4]=[CH:3]1.C([Li])(C)(C)C.[C:18](OC)(=[O:23])[C:19]([O:21][CH3:22])=[O:20]>C1COCC1>[CH3:22][O:21][C:19](=[O:20])[C:18]([C:9]1[CH:8]=[C:7]([CH3:12])[CH:6]=[C:5]2[C:10]=1[N:2]([CH3:1])[CH:3]=[CH:4]2)=[O:23]

Participants

5

Reactant 3

HCID 11120Dimethyl oxalateHCID 219499621,5-Dimethyl-7-bromoindoleHCID 178418306HCID 178418306, compound

Product 1

HCID 69642519(1,5-dimethyl-1H-indol-7-yl)-oxo-acetic acid methyl esterYield 95.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1,5-dimethyl-7-bromoindole (4.27 g, 19.05 mmol) in THF (130 mL) was cooled to −78° C. and a solution of tert-butyl lithium in pentanes (1.7 M, 24.6 mL, 41.8 mmol) added dropwise over 30 min. After 30 min at −78° C., the mixture was treated with dimethyl oxalate (5.62 g, 47.6 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 (4.2 g, 95%) as bright yellow oil. 1H NMR (400 MHz, CDCl3) δ 2.46 (s, 3H), 3.85 (s, 3H), 4.01 (s, 3H), 6.51 (dd, J1=1.17 Hz, J2=3.13 Hz, 1 H), 7.06 (d, J=3.13 Hz, 1H), 7.36 (s, 1H), 7.69 (s, 1H); MS (ES, m/z): C13H13NO3: 232.19 (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-81a0d693fc5944a784253f5101e4458d
Source dataset
uspto-grants-2006_09
Patent number
US07109229B2

Reaction notes

Loading…