Water → 2-(1-Methyl-1H-indol-3-YL)-2-oxoacetic acid methyl ester

HRID 1017587Notes

Reaction equation

HRID 1017587 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3]1.[C:11](Cl)(=[O:15])[C:12](Cl)=[O:13].[CH3:17][O-:18].[Na+].O>CCOCC>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([C:11](=[O:15])[C:12]([O:18][CH3:17])=[O:13])=[CH:3]1

Participants

6

Reactant 4

HCID 962WaterHCID 117811-MethylindoleHCID 65578Oxalyl chlorideHCID 10942334Sodium Methoxide

Product 1

HCID 44536752-(1-Methyl-1H-indol-3-YL)-2-oxoacetic acid methyl esterYield 82.8%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-65 °C

Procedure

To a 0° C. solution of 1-methylindole (7.58 g, 50 mmoles) in dry ether (75 mL) under argon was added oxalyl chloride (4.36 mL, 50 mmoles) slowly. The resulting suspension was stirred for 30 minutes. After cooling to −65° C, sodium methoxide (22.9 mL, 100 mmoles, 25% in MeOH) was added dropwise at a rate to maintain −60° C. After the addition was complete, the reaction was allowed to warm to room temperature and stir for 2 hours. Water was added (30 mL) and the crude mixture was stirred then filtered. The resultant solid was washed with water, ether and then air dried. Purification of the crude product via flash chromatography (SiO2, 20% to 40% ethyl acetate/Hexane—gradient) provided methyl (1-methyl-1H-indol-3-yl)(oxo)acetate as a solid (9 g, 41.4 mmoles).

Workup

  1. temperatureto maintain −60° C
  2. additionAfter the addition
  3. temperatureto warm to room temperature
  4. stirringstir for 2 hours
  5. filtrationthen filtered
  6. washThe resultant solid was washed with water, ether
  7. customair dried
  8. customPurification of the crude product via flash chromatography (SiO2, 20% to 40% ethyl acetate/Hexane—gradient)

Sources & evidence

ORD record
ord-c499bff7f78f4fd4880487ae88a57099
Source dataset
uspto-grants-2002_11
Patent number
US06479490B2

Reaction notes

Loading…