* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With potassium carbonate; In acetone; at 20℃; for 16.0h;Heating / reflux;
Preparation of 4-methoxy-1H-indole-6-carboxylic Acid Methyl Ester: Methyl iodide (0.72 mL, 11.5 mmol, 1.1 equiv.) was added dropwise, over 10 minutes, to a stirred solution of <strong>[77140-48-8]4-hydroxy-1H-indole-6-carboxylic acid methyl ester</strong> (2 g, 10.5 mmol, 1 equiv.) and potassium carbonate (1.3 g, 15.7 mmol, 1.5 equiv.) in acetone (20 mL) at room temperature and the mixture was heated at reflux for 16 hours. The solvent was removed under vacuum, the residue dissolved in ethyl acetate (20 mL) and washed with saturated aqueous solution of NaHCO3 (20 mL) and water (20 mL). The organic layer was dried over Na2SO4 and the solvent removed under vacuum to afford 4-methoxy-1H-indole-6-carboxylic acid methyl ester, 1.1 g (49% yield). LC (at)215 nm; Rt 1.23: 91%, m/z (ES+): 206 (M+H+.); deltaH (400 MHz; MeOD) 7.74 (1H, s), 7.15 (1H, m), 7.03 (1H, d), 6.46 (1H, m), 3.86 (3H, s), 3.80 (3H, s).
a) 4-Ethoxy-1-ethyl-1H-indole-6-carboxylic acid methyl ester. Potassium tert-butylate (3.13 g, 27.9 mmol) was added over 30 min to a solution of <strong>[77140-48-8]4-hydroxy-1H-indole-6-carboxylic acid methyl ester</strong> (4.85 g, 25.4 mmol) and bromoethane (3.04 g, 27.9 mmol) at 0 C. After 75 min the solvent was evaporated and the residue partitioned between ethyl acetate and water. The organic layer was dried (MgSO4), and evaporated. Column chromatography (SiO2; hexane/ethyl acetate 3:1) afforded the title compound (550 mg, 9%). Light yellow solid. MS (EI): 247 (M+)
With potassium carbonate; In water; N,N-dimethyl-formamide;
22.2 g. of the <strong>[77140-48-8]4-hydroxy-6-methoxycarbonyl-indole</strong> thus obtained, 16.5 g. dry potassium carbonate and 15.9 ml. benzyl chloride were heated for 3 hours to 80-90 C., while stirring, in 200 ml. anhydrous dimethyl formamide. About 100-150 ml. dimethyl formamide were evaporated off in a vacuum and the residue is mixed with water and diethyl ether. The ethereal phase was separated off and the aqueous phase extracted several times with diethyl ether. The combined ethereal extracts were dried, clarified with active charcoal and evaporated. The crystallized residue was, with the addition of active charcoal, recrystallized from ethanol. There were obtained 18.0 g. (53.5% of theory) of almost colorless crystals; m.p. 160 - 162 C. A solution of 24.5 g. of the 4-benzyloxy-6-methoxycarbonylindole thus obtained in 150 ml. anhydrous tetrahydrofuran was added dropwise, while stirring and cooling to 15 - 20 C., into a suspension of 5.3 g. lithium aluminium hydride in 150 ml. anhydrous tetrahydrofuran.
With potassium carbonate; In water; N,N-dimethyl-formamide;
22.2 g. of the <strong>[77140-48-8]4-hydroxy-6-methoxycarbonyl-indole</strong> thus obtained, 16.5 g. dry potassium carbonate and 15.9 ml. benzyl chloride were heated for 3 hours to 80-90 C., while stirring, in 200 ml. anhydrous dimethyl formamide. About 100-150 ml. dimethyl formamide were evaporated off in a vacuum and the residue is mixed with water and diethyl ether. The ethereal phase was separated off and the aqueous phase extracted several times with diethyl ether. The combined ethereal extracts were dried, clarified with active charcoal and evaporated. The crystallized residue was, with the addition of active charcoal, recrystallized from ethanol. There were obtained 18.0 g. (53.5% of theory) of almost colorless crystals; m.p. 160-162 C. A solution of 24.5 g. of the 4-benzyloxy-6-methoxycarbonylindole thus obtained in 150 ml. anhydrous tertrahydrofuran was added dropwise, while stirring and cooling to 15-20 C., into a suspension of 5.3 g. lithium aluminum hydride in 150 ml. anhydrous tetrahydrofuran.
4-(2,3-epoxypropoxy)-6-hydroxymethyl-indole[ No CAS ]
[ 61545-25-3 ]
[ 41123-14-2 ]
[ 77140-48-8 ]
Yield
Reaction Conditions
Operation in experiment
With benzoic acid; In ethyl acetate; tert-butylamine; isopropyl alcohol;
EXAMPLE 15 Preparation of 4-(2-hydroxy-3-tert.-butylaminopropoxy)-6-hydroxymethyl-indole 5 g. 4-(2,3-epoxypropoxy)-6-hydroxymethyl-indole were dissolved in 25 ml. tert.-butylamine. The mixture was left to stand for 2 days at ambient temperature, subsequently boiled gently for about an hour and then evaporated in a vacuum. The residue was partitioned between dilute acetic acid and diethyl ether. The ethereal phase was discarded and the acetic acid solution was rendered alkaline and then shaken out with ether. After drying and evaporating the ethereal phase, the base thereby obtained was recrystallized from a little ethyl acetate/diethyl ether (3.3 g. of base; m.p. 129 - 131 C). 3.0 g. of this base were dissolved in a mixture of about 100 ml. ethyl acetate and 20 ml. isopropanol. Upon the addition of 1.2 g. benzoic acid, the benzoate slowly precipitates out. After filtering off with suction and drying, there were obtained 3.4 g. (41% of theory) 4-(2-hydroxy-3-tert.-butylaminopropoxy)-6-hydroxymethyl-indole in the form of its benzoate; m.p. 190 - 191 C. The 4-(2,3-epoxypropoxy)-6-hydroxymethyl-indole used as starting material is prepared as follows: 4-Acetoxy-6-methoxycarbonyl-indole, obtained by the modification of a process described by N.R. El-Rayyes (J. prakt. Chem., 315, 295/1973), was saponified with sodium methylate, with the exclusion of oxygen, to give 4-hydroxy-6-methoxycarbonyl-indole.
With benzoic acid; In ethyl acetate; tert-butylamine; isopropyl alcohol;
EXAMPLE 15 Preparation of 4-(2-hydroxy-3-tert.-butylaminopropoxy)-6-hydroxymethyl-indole 5 g. 4-(2,3-epoxypropoxy)-6-hydroxymethyl-indole were dissolved in 25 ml. tert.-butylamine. The mixture was left to stand for 2 days at ambient temperature, subsequently boiled gently for about an hour and then evaporated in a vacuum. The residue was partitioned between dilute acetic acid and diethyl ether. The ethereal phase was discarded and the acetic acid solution was rendered alkaline and then shaken out with ether. After drying and evaporating the ethereal phase, the base thereby obtained was recrystallized from a little ethyl acetate/diethyl ether (3.3 g. of base; m.p. 129-131 C.). 3.0 g. of this base were dissolved in a mixture of about 100 ml. ethyl acetate and 20 ml. isopropanol. Upon the addition of 1.2 g. benzoic acid, the benzoate slowly precipitates out. After filtering off with suction and drying, there were obtained 3.4 g. (41% of theory) 4-(2-hydroxy-3-tert.-butylaminopropoxy)-6-hydroxymethyl-indole in the form of its benzoate; m.p. 190-191 C. The 4-(2,3-epoxypropoxy)-6-hydroxymethyl-indole used as starting material is prepared as follows: 4-Acetoxy-6-methoxycarbonyl-indole, obtained by the modification of a process described by N. R. El-Rayyes (J. prakt. Chem., 315, 295/1973), was saponified with sodium methylate, with the exclusion of oxygen, to give 4-hydroxy-6-methoxycarbonyl-indole.
methyl 4-isopropoxy-1H-indole-6-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
77%
With potassium carbonate; In N,N-dimethyl-formamide; at 0℃; for 16.0h;Inert atmosphere;
Potassium carbonate (651 mg, 4.71 mmol) and 2-iodopropane (275 mg, 1.57 mmol) were addedto a solution of <strong>[77140-48-8]methyl 4-hydroxy-1H-indole-6-carboxylate</strong> (CAS-RN 77 140-48-8; 300 mg, 1.57mmol) in N,N-dimethylformamide (9 mL) at 0C. The reaction mixture was stuffed for 16 h at0C, then partitioned between water and ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, filtered and evaporated to give a light brown oil. Chromatography (silica gel; heptane-ethyl acetate gradient) produced the title compound (280mg, 77%). White solid, MS: 232.2 (M-H).
An oven-dried flask was charged with commercial <strong>[77140-48-8]methyl 4-hydroxyindole-6-carboxylate</strong> (50 mg, 0.26 mmol) in anhydrous DMF (1 mL) at 0 C. To this solution was added NaH (60% in mineral oil, 31 mg, 0.79 mmol) and the solution was stirred for 30 min at 0 C. After CH3I (40 muL, 0.63 mmol) was added dropwise to the solution via syringe, the solution was allowed to equilibrate to rt overnight. The reaction was quenched with the addition of H2O (3 mL) and the mixture was extracted with EtOAc (5*). The organic extracts were combined, dried over Na2SO4, and filtered, and the filtrate was concentrated under reduced pressure. Final purification using an ISCO Combiflash Rf chromatography gradient (0-20% EtOAc in hexanes) afforded the dimethylated compound 29 (47.8 mg, 83%) as a yellow oil: 1H NMR (500 MHz, CDCl3) delta 7.78 (s, 1H), 7.20 (s, 1H), 7.11 (d, J = 3.0 Hz, 1H), 6.61 (d, J = 2.7 Hz, 1H), 4.00 (s, 3H), 3.95 (s, 3H), 3.84 (s, 3H). 30
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