Reaction #1265409

Reaction equation

2-chloroethyl acetate

sodium hydride

3,4-dihydroquinolin-2(1H)-one

→

1-(2-acetoxyethyl)-3,4-dihydroquinolin-2(1H)-one

Yield 64.4%

Solvents

dimethyl formamide

dimethyl formamide

dimethyl formamide

Conditions

Workup

1. 1
   Otherwas kept at 15-18° C.
2. 2
   TemperatureThe resulting mixture was heated at 80° C. for 2½ h
3. 3
   Temperaturecooled
4. 4
   workup.ADDITIONpoured onto ice
5. 5
   ExtractionThe aqueous phase was extracted with ethyl acetate
6. 6
   Washthe combined organic phases were washed with brine
7. 7
   Dryingdried (MgSO4)
8. 8
   Concentrationconcentrated in vacuo
9. 9
   OtherThe crude product was purified by flash chromatography on silicagel (eluent: ethyl acetate/heptane 1:1)

Procedure

A suspension of sodium hydride (3.0 g, 60% in mineral oil) and dimethyl formamide (100 mL) was kept at 15-18° C. followed by the addition of a solution of 3,4-dihydroquinolin-2(1H)-one (10.0 g) in dimethyl formamide (150 mL). The resulting mixture was stirred at room temperature for 60 min followed by the addition of a solution of 2-chloroethyl acetate (10.0 g) in dimethyl formamide (50 mL) at a temperature of 20° C. The resulting mixture was heated at 80° C. for 2½ h, cooled and poured onto ice. The aqueous phase was extracted with ethyl acetate, and the combined organic phases were washed with brine, dried (MgSO4) and concentrated in vacuo. The crude product was purified by flash chromatography on silicagel (eluent: ethyl acetate/heptane 1:1) to give crude 1-(2-acetoxyethyl)-3,4-dihydroquinolin-2(1H)-one (10.2 g). A mixture of crude 1-(2-acetoxyethyl)-3,4-dihydroquinolin-2(1H)-one, sodium methanolate (2.5 mL, 30% in methanol) and methanol (250 mL) was stirred at room temperature for 16 h and subsequently concentrated in vacuo. The residue was purified by flash chromatography on silicagel (eluent: ethyl acetate/heptane 1:1) to give the corresponding alcohol as a red crystalline compound (4.9 g). This alcohol was dissolved in tetrahydrofuran (100 mL) followed by the addition of triethylamine (8.2 mL). The resulting mixture was cooled to 5-6° C. followed by the addition of a solution of methane sulfonic acid chloride (2 mL) in tetrahydrofuran (25 mL). The mixture was filtered and evaporated to dryness in vacuo. The residue was dissolved in dimethyl formamide (50 mL) followed by addition of lithium chloride (4.9 g), and the resulting mixture was heated at 70° C. for 5 min. The mixture was poured onto brine, and the aqueous phase was extracted with ethyl acetate. The combined organic phases were dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash chromatography on silicagel (eluent: ethyl acetate/heptane 1:1) to give the product as a red oil (2.9 g).

Source