Methanol → Methyl 2-(4-Methoxy-3-indolyl)-2-oxoacetate

HRID 2215769Notes

Reaction equation

HRID 2215769 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[CH:5]=[CH:6][NH:7]2.C(Cl)(=O)[C:13](Cl)=[O:14].[CH3:18][O-:19].[Na+].[CH3:21][OH:22]>CCOCC.CCOC(C)=O>[CH3:18][O:19][C:13](=[O:14])[C:21]([C:5]1[C:4]2[C:8](=[CH:9][CH:10]=[CH:11][C:3]=2[O:2][CH3:1])[NH:7][CH:6]=1)=[O:22]

Participants

7

Reactant 4

HCID 887MethanolHCID 65578Oxalyl chloride2×HCID 1383634-Methoxy-1H-indoleHCID 10942334Sodium Methoxide

Product 1

HCID 53419524Methyl 2-(4-Methoxy-3-indolyl)-2-oxoacetateYield 51%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 4-methoxy-indole (1.04 g, 7.07 mmol) in Et2O (150 mL) cooled to 0–5° C. was treated with oxalyl chloride (0.7 mL, 8.0 mmol). After 1h, the orange solution was allowed to warm to room temperature and stirred 2.5 h. Additional oxalyl chloride (0.25 mL, 2.9 mmol) was then added. After stirring 3 h at room temperature, the mixture was cooled to −78° C. and a 25% solution of sodium methoxide in methanol (5.4 mL, 23.4 mmol) added. The suspension was warmed to room temperature, stirred 3 h and neutralized by the addition of pH 7 buffer. The mixture was poured into EtOAc and the organic layer was separated and washed with saturated aq sodium bicarbonate, brine, dried (MgSO4) and concentrated to a dark oil. Trituration with Et2O (75 mL) afforded the title compound as a green solid (0.848 g, 51%) which was used without further purification. 1H NMR (400 MHz, DMSO-d6) 12.40 (s, 1H), 8.20 (d, J=4.3 Hz, 1H), 7.19 (dd, J=7.8, 7.8 Hz, 1H), 7.12 (d, J=7.8 Hz, 1H), 6.73 (d, J=7.8 Hz, 1H), 3.84 (s, 3H), 3.82 (s, 3H). MS (electrospray, m/z) 234.0 (M++1), 232.1 (M−−1).

Workup

  1. stirringAfter stirring 3 h at room temperature
  2. temperaturethe mixture was cooled to −78° C.
  3. temperatureThe suspension was warmed to room temperature
  4. stirringstirred 3 h
  5. additionneutralized by the addition of pH 7 buffer
  6. customthe organic layer was separated
  7. washwashed with saturated aq sodium bicarbonate, brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated to a dark oil

Sources & evidence

ORD record
ord-910ab5c1b864416b9430f07d4ec6c656
Source dataset
uspto-grants-2006_09
Patent number
US07109229B2

Reaction notes

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