Reaktion #314550

Reaktionsgleichung

indole

ethyl magnesium bromide

tetrahydrofuran

product

2,2,3,3-tetramethylcyclopropanecarbonyl chloride

→

1H-indol-3-yl(2,2,3,3-tetramethylcyclopropyl)methanone

Ausbeute 42.0%

1-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indole

Ausbeute 27.0%

Lösungsmittel

dichloromethane

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONAfter the addition
2. 2
   workup.ADDITIONwas added
3. 3
   workup.STIRRINGThe mixture was stirred for 6 h
4. 4
   Sonstigethen was quenched with 50 mL saturated aqueous NH4Cl
5. 5
   workup.ADDITIONdiluted with 50 mL dichloromethane
6. 6
   SonstigeThe layers were separated
7. 7
   Extraktionthe aqueous layer was extracted with 3×30 mL dichloromethane
8. 8
   WaschenThe combined organics were washed with 1×20 mL H2O
9. 9
   Trocknenthen were dried over anhydrous Na2SO4
10. 10
    Filtrationfiltered
11. 11
    Einengenconcentrated under reduced pressure
12. 12
    SonstigeThe crude material was purified via column chromatography (SiO2, 50% ethyl acetate:hexanes)

Vorschrift

To a solution of indole (Aldrich, 11 g, 95 mmol) in 30 mL dichloromethane at ambient temperature was added 105 mL of a 1 M solution of ethyl magnesium bromide in tetrahydrofuran (THF) (105 mmol) dropwise via syringe pump. After the addition was complete, the solution was stirred for 15 min at which time ZnCl2 (14 g, 105 mmol) was added. The mixture stirred for an additional 30 min then the product of Example 1A (95 mmol) in 50 mL dichloromethane was added via cannula. The mixture was stirred for 6 h then was quenched with 50 mL saturated aqueous NH4Cl and diluted with 50 mL dichloromethane. The layers were separated and the aqueous layer was extracted with 3×30 mL dichloromethane. The combined organics were washed with 1×20 mL H2O then were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified via column chromatography (SiO2, 50% ethyl acetate:hexanes) to give 9.7 g of the major regioisomer 1H-indol-3-yl(2,2,3,3-tetramethylcyclopropyl)methanone (40 mmol, 42% yield) and 6.1 g of the minor regioisomer of 1-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indole (25 mmol, 27% yield). MS (major and minor regioisomers) (DCI/NH3) m/z 242 (M+H)+.

Quelle