Reaction #6325

Reaction equation

ammonium hydroxide

Magnesium

ethyl indole-2-carboxylate

hydrochloric acid

sodium bisulfate

ammonium hydroxide

→

title compound

(±) Methyl indoline-2-carboxylate

Solvents

methylene chloride

methanol

Conditions

Workup

1. 1
   Otherplaced in an ice bath
2. 2
   Otherrises to 35°
3. 3
   workup.WAITsubsides to 0° within one hour
4. 4
   workup.STIRRINGAfter stirring for another two hours at 0°
5. 5
   ExtractionThis mixture is then extracted with methylene chloride
6. 6
   DryingThe combined organic layers are dried over magnesium sulfate
7. 7
   Concentrationconcentrated
8. 8
   Otherto provide
9. 9
   workup.ADDITIONa mixture of an oil with some solid
10. 10
    OtherFrom this mixture an off white solid is obtained
11. 11
    Washby washing the mixture with ethyl acetate/hexane (25/75)
12. 12
    OtherA small sample (620 mg) of the recovered oil is purified
13. 13
    WashThe column is eluted with ethyl acetate/hexane (1/3, 11; 1/1, 0.51)
14. 14
    Othercollecting 25 ml fractions
15. 15
    Concentrationconcentrated

Procedure

Magnesium turnings (6.449 g) are added to a suspension of ethyl indole-2-carboxylate (I, Aldrich, 25.083 g) in methanol (freshly opened, HPLC grade, 350 ml). The mixture is stirred at 24° for 10 minutes, then placed in an ice bath. After stirring for 15 minutes in the ice bath, there is much gas evolution and the temperature rises to 35° but then subsides to 0° within one hour. After stirring for another two hours at 0°, cold hydrochloric acid (3N, 250 ml) is added slowly. The mixture turns to a gel. The gel is then treated with ammonium hydroxide (3N, 250 ml). Upon adding methylene chloride to the gel, it forms an inseparable suspension. The crude mixture is made acidic (pH 1) with aqueous sodium bisulfate (10%) then made alkaline (pH 8-9) with ammonium hydroxide (3N). This mixture is then extracted with methylene chloride. The combined organic layers are dried over magnesium sulfate and concentrated to provide a mixture of an oil with some solid. From this mixture an off white solid is obtained by washing the mixture with ethyl acetate/hexane (25/75). A small sample (620 mg) of the recovered oil is purified by passing it over a silica column (20.5×2.5 cm, 40-63 μ). The column is eluted with ethyl acetate/hexane (1/3, 11; 1/1, 0.51) collecting 25 ml fractions. The appropriate fractions are pooled and concentrated to give the title compound, NMR (CDCl3, 300 MHz) 7.04, 6.71, 4.46, 4.37, 3.74 and 3.35 δ; CMR (CDCl3, 75.47 MHz) 33.69, 52.42, 59.81, 110.05, 119.48, 124.45, 126.63, 127.67, 150.03 and 174.62 δ; IR (CHCl3) 3480, 3390, 2970, 1730, 1605, 1480, 1460, 1430 and 1200 cm-1 ; MS (m/e) 177, 147, 129, 119, 118, 117, 91, 86, 84 and 49, exact mass calcd for C10H11NO2 (177.0790), found 177.0789; TLC (ethyl acetate/hexane, 1/1) Rf =0.55 (UV).

Source