Methyl iodide → tert-butyl 2-(1-ethoxy-1-oxopropan-2-yl)-1H-indole-1-carboxylate

HRID 1908516Notes

Reaction equation

HRID 1908516 reaction equation
[CH2:1]([O:3][C:4](=[O:22])[CH2:5][C:6]1[N:7]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C:8]2[C:13]([CH:14]=1)=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH3:2].[CH3:23][Si](C)(C)N[Si](C)(C)C.[K].CI>C1COCC1>[CH2:1]([O:3][C:4](=[O:22])[CH:5]([C:6]1[N:7]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C:8]2[C:13]([CH:14]=1)=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH3:23])[CH3:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 45051783Silanamine, 1,1,1-trimethyl-N-(trimethylsilyl)-, potassium saltHCID 53419936tert-Butyl 2-(2-ethoxy-2-oxoethyl)-1H-indole-1-carboxylate

Product 1

HCID 59129246tert-butyl 2-(1-ethoxy-1-oxopropan-2-yl)-1H-indole-1-carboxylateYield 89.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

tert-Butyl 2-(2-ethoxy-2-oxoethyl)-1H-indole-1-carboxylate (3.0 g, 9.9 mmol) was added to anhydrous THF (29 mL) and cooled to −78° C. A 0.5M solution of potassium hexamethyldisilazane (20 mL, 9.9 mmol) was added slowly such that the internal temperature stayed below 60° C. Stirring was continued for 1 h at −78° C. Methyl iodide (727 μL, 11.7 mmol) was added to the mixture. The mixture was stirred for 30 minutes at room temperature. The mixture was quenched with sat. aq. ammonium chloride and partitioned between water and dichloromethane. The aqueous phase was extracted with dichloromethane and the combined organic phases were dried over Na2SO4 and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (ethylacetate/hexane=1/9) to give tert-butyl 2-(1-ethoxy-1-oxopropan-2-yl)-1H-indole-1-carboxylate (2.8 g, 88%).

Workup

  1. customstayed below 60° C
  2. stirringThe mixture was stirred for 30 minutes at room temperature
  3. customThe mixture was quenched with sat. aq. ammonium chloride
  4. custompartitioned between water and dichloromethane
  5. extractionThe aqueous phase was extracted with dichloromethane
  6. dry with materialthe combined organic phases were dried over Na2SO4
  7. customevaporated under reduced pressure
  8. customThe residue was purified by column chromatography on silica gel (ethylacetate/hexane=1/9)

Sources & evidence

ORD record
ord-f80faf28cdea434b9d3d5f8b73120f5d
Source dataset
uspto-grants-2013_12
Patent number
US08598181B2

Reaction notes

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