Réaction #6332

Équation de réaction

N-[(7-Bromo-9,9a-dihydro-3-oxo-1H,3H-oxazolo[3,4-a]indol-1-yl)methyl]acetamide

N-[(7-bromo-9,9a-dihydro-3-oxo-1H,3H-oxazolo[3,4-a]indol-1-yl)methyl]acetamide

phenylboronic acid

sodium carbonate

→

title compound

N-[(7-phenyl-9,9a-dihydro-3-oxo-1H,3H-oxazolo[3,4-a]indol-1-yl)methyl]acetamide

Solvants

tetrahydrofuran

methylene chloride

Conditions de réaction

Traitement

1. 1
   TempératureThe mixture is warmed for 15.5 hours in an oil bath at 68°
2. 2
   AutreThe mixture is then partitioned between aqueous sodium carbonate (2M, 2 ml) and methylene chloride (3 ml)
3. 3
   AutreAfter separation of the layers
4. 4
   Extractionthe aqueous phase is extracted with additional methylene chloride (3×2 ml)
5. 5
   Séchagedried over magnesium sulfate
6. 6
   Concentrationconcentrated
7. 7
   Autreto provide a solid
8. 8
   Lavageeluted with ethyl acetate/methanol gradient
9. 9
   Concentrationconcentrated

Mode opératoire

(±) (1S,9aS/1R,9aR) N-[(7-Bromo-9,9a-dihydro-3-oxo-1H,3H-oxazolo[3,4-a]indol-1-yl)methyl]acetamide (EXAMPLE 24, 129 mg) is dissolved in tetrahydrofuran (1 ml). To this mixture palladium tetrakis(triphenylphosphine) (22 mg), phenylboronic acid (61 mg) and aqueous sodium carbonate (2M, 0.45 ml) is added. The mixture is warmed for 15.5 hours in an oil bath at 68°. The mixture is then partitioned between aqueous sodium carbonate (2M, 2 ml) and methylene chloride (3 ml). After separation of the layers, the aqueous phase is extracted with additional methylene chloride (3×2 ml). The organic layers are combined, dried over magnesium sulfate and concentrated to provide a solid. This solid is taken up in methylene chloride and placed on a 20.5 cm×2.5 cm, 40-63μ silica column and eluted with ethyl acetate/methanol gradient. The appropriate fractions are pooled and concentrated to give the title compound, mp 181°-183°; NMR (CDCl3, 300 MHz) 7.43, 6.08, 4.53, 4.54, 3.83, 3.70, 3.35, 3.17 and 2.07 δ.

Source