|
With sodium hydroxide; water In 1,4-dioxane; methanol at 60℃; |
21 Reference example 21; 2-methyl-1H-indole-4-carboxylic acid
Reference example 21 2-methyl-1H-indole-4-carboxylic acid 5N sodium hydroxide solution (10ml) was added to methanol dioxane(10ml+10ml) solution containing the compound (4.3g) prepared according to reference example 20, which was stirred at 60°C over night. 2N hydrochloric acid was added to the reaction solution, which was extracted by ethyl acetate.. The water layer was extracted by ethyl acetate and the mixed organic layer was sequentially washed with water and saturated brine and dried, and then concentrated by vacuum concentration.. The residue was purified by silica gel column chromatography (chloroform: methanol=85:1) to give a title compound (1.6g) having the following physical properties. TLC:Rf0.48 (chloroform: methanol=9:1); NMR(CDCl3):δ 8-1,4-8.04 (br, 1H), 7.94 (dd, J = 7.5, 0.9 Hz, 1H), 7.52 (m, 1H), 7.18 (t, J = 7.5 Hz, 1H), 6.94 (m, 1H), 2.52 (s, 3H). |
|
With hydrogenchloride; sodium hydroxide; sodium chloride In methanol-dioxane |
R.10 2-Methylindole-4-carboxylic Acid
REFERENCE EXAMPLE 10 2-Methylindole-4-carboxylic Acid To a solution of 2-methylindole-4-carboxylic acid methyl ester (4.3 g; prepared in Reference Example 9) in methanol-dioxane (10 ml+10 ml) was added 5N aqueous solution of sodium hydroxide (10 ml), and the mixture was stirred at 60° C. overnight. To the reaction solution was added 2N hydrochloric acid, and then extracted with ethyl acetate. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with water and a saturated aqueous solution of sodium chloride, successively, dried and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (chloroform-methanol) to give the title compound (1.6 g) having the following physical data. TLC: Rf 0.48(chloroform:methanol=9:1); NMR (CDCl3): δ 8.14-8.04 (br, 1H), 7.93 (dd, 1H), 7.52 (m, 1H), 7.18 (dd, 1H), 6.94 (m, 1H), 3.71 (s, 3H). |
| 106 mg |
With water; potassium hydroxide In ethanol at 80℃; Inert atmosphere; |
9.2; 10.2 [88] Step2. 2-Methyl-lH-indole-4-carboxylic
[89] Into a 100-mL round-bottom flask, was placed methyl 2-methyl-lH-indole-4-carboxylate (0.3 g, crude,), ethanol (10 mL), potassium hydroxide (0.445 g, 7.93 mmol) and water (5 mL). The resulting solution was stirred overnight at 80 °C. After cooling down to room temperature, the reaction mixture was diluted with water (100 mL), and extracted with ethyl acetate (60 mL). The pH value of the aqueous phase was adjusted to 5-6 with HC1 (IN). The resulting solution was extracted with ethyl acetate (60 mL). The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. The residue was purified by Pre-TLC with ethyl acetate/petroleum ether (1/1). This resulted in 106 mg of the title compound as a red solid. MS (ES, m/z) [M+H]+: 176. |
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
