Diethyl Ether → Methyl [2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-5-chloro-1h-indol-3-yl](oxo)acetate

HRID 2301668Notes

Reaction equation

HRID 2301668 reaction equation
[Si:1]([O:8][CH2:9][C:10]1[NH:11][C:12]2[C:17]([CH:18]=1)=[CH:16][C:15]([Cl:19])=[CH:14][CH:13]=2)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[C:20](Cl)(=[O:24])[C:21](Cl)=[O:22].C[CH2:27][O:28]CC>>[Si:1]([O:8][CH2:9][C:10]1[NH:11][C:12]2[C:17]([C:18]=1[C:20](=[O:24])[C:21]([O:28][CH3:27])=[O:22])=[CH:16][C:15]([Cl:19])=[CH:14][CH:13]=2)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

4

Reactant 3

HCID 3283Diethyl EtherHCID 65578Oxalyl chlorideHCID 701602652-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-5-chloro-1h-indole

Product 1

HCID 90772388Methyl [2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-5-chloro-1h-indol-3-yl](oxo)acetateYield 65%

Conditions

Temperature
0 °C

Procedure

2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-5-chloro-1H-indole (1 eq) was dissolved in ether (0.38M) and the solution was cooled to 0° C. Oxalyl chloride (2M in CH2Cl2) (1.2 eq) was added to the above cold solution with vigorous stirring. Precipitation occurred. The suspension was kept stirred at 0° C. for 30 minutes. Then MeOH (3/5 volume of oxalyl chloride solution) was added to the reaction mixture, followed by NEt3 (6/5 volume of oxalyl chloride solution). The resulting mixture was then diluted with MeOH (6/5 volume of oxalyl chloride solution) before it was poured into water (4× volume of oxalyl chloride solution). Extract with EtOAc. Organic phase washed with brine, dried over Na2SO4, and concentrated to give methyl [2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-5-chloro-1H-indol-3-yl](oxo)acetate (brown solid) in 65% yield.

Workup

  1. customPrecipitation
  2. additionThen MeOH (3/5 volume of oxalyl chloride solution) was added to the reaction mixture
  3. additionThe resulting mixture was then diluted with MeOH (6/5 volume of oxalyl chloride solution) before it
  4. additionwas poured into water (4× volume of oxalyl chloride solution)
  5. extractionExtract with EtOAc
  6. washOrganic phase washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-592bdac6f02f4039b1f9e93ca5100b32
Source dataset
uspto-grants-2002_12
Patent number
US06500853B1

Reaction notes

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