Réaction #661783

Équation de réaction

4-methyl-1-naphthoyl chloride

4-(2-(5-methoxy-2-methyl-1H-indol-1-yl)ethyl)morpholine

ethyl aluminum dichloride

→

(5-methoxy-2-methyl-1-(2-morpholinoethyl)-1H-indol-3-yl)(4-methylnaphthalen-1-yl)methanone

Solvants

CH2Cl2

Conditions de réaction

Traitement

1. 1
   AutreThe reaction mixture was then partitioned between ethyl acetate and cold H2O
2. 2
   Extractionthe aqueous layer extracted twice with ethyl acetate
3. 3
   ExtractionThe combined organic extract
4. 4
   Lavagewas washed successively with H2O, 10% K2CO3, and brine
5. 5
   Séchagedried over MgSO4
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated in vacuo
8. 8
   AutreThe crude product was purified via silica gel chromatography
9. 9
   Autreto give CBX001 (107 mg, 0.24 mmol)

Mode opératoire

To a solution of 4-methyl-1-naphthoyl chloride (84 mg, 0.41 mmol) and 4-(2-(5-methoxy-2-methyl-1H-indol-1-yl)ethyl)morpholine (120 mg, 0.44 mmol) in 8 mL CH2Cl2 at −70° C. was added dropwise ethyl aluminum dichloride (0.5 mL, 0.90 mmol, 1.8 M in toluene). The reaction mixture was allowed to slowly warm to room temperature overnight. The reaction mixture was then partitioned between ethyl acetate and cold H2O, and the aqueous layer extracted twice with ethyl acetate. The combined organic extract was washed successively with H2O, 10% K2CO3, and brine, dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified via silica gel chromatography using a gradient from 0 to 10% MeOH in CH2Cl2 to give CBX001 (107 mg, 0.24 mmol). 1H NMR (500 MHz, CDCl3, δ): 2.37 (s, 3H), 2.42-2.55 (m, 4H), 2.66 (t, J=6.9 Hz, 2H), 2.78 (s, 3H), 3.59 (s, 3H), 3.68 (t, J=4.2 Hz, 4H), 4.17 (t, J=6.9 Hz, 2H), 6.84 (dd, J=8.8 Hz, 2.4 Hz, 1H), 6.92 (d, J=2.2 Hz, 1H), 7.20 (d, J=8.8 Hz, 1H), 7.38 (d, J=7.0 Hz, 1H), 7.41-7.50 (m, 2H), 7.55 (t, J=7.2 Hz, 1H), 8.08 (d, J=8.4 Hz, 1H), 8.15 (d, J=8.3 Hz, 1H). 13C NMR (500 MHz, CDCl3, δ): 13.14, 20.21, 41.74, 53.90, 54.49, 55.80, 57.81, 67.29, 103.91, 110.33, 112.67, 115.61, 124.69, 125.76, 126.30, 126.59, 126.91, 128.42, 130.86, 131.35, 133.25, 136.92, 139.50, 145.98, 156.28, 193.91. MS m/z 443.4 [M+H]+.

Source