Reaction #48118

Reaction equation

5-hydroxyindole-2-carboxylic acid ethyl ester

1-isopropylpiperidin-4-ol

1-Isopropyl-piperidin-4-ol

intermediate 1

1-Isopropyl-piperidin-4-ol

triphenylphosphine

di-tert-butylazodicarboxylate

→

desired product

Yield 66.9%

5-(1-Isopropyl-piperidin-4-yloxy)-1H-indole-2-carboxylic acid ethyl ester

Yield 66.9%

Solvents

tetrahydrofuran

tetrahydrofuran

Conditions

Workup

1. 1
   Otherthen evaporated to dryness in vacuo
2. 2
   Otherpurified on silica
3. 3
   Washeluting with a gradient of solvent from dichloromethane/ethyl acetate 19:1 to dichloromethane/methanol/ammonium hydroxide 95:5:0.25
4. 4
   OtherOne fraction was isolated
5. 5
   Otherdried in vacuo

Procedure

To a cold (0° C.) solution of 5-hydroxyindole-2-carboxylic acid ethyl ester (purchased at Biosynth, ref H-6350, 20 g, 1.0 eq.), 1-isopropylpiperidin-4-ol (intermediate 1, step 1, 16.75 g, 1.2 eq.) and triphenylphosphine (30.68 g, 1.2 eq.) in tetrahydrofuran (500 mL) was slowly added a solution of di-tert-butylazodicarboxylate (26.93 g, 1.2 eq.) in tetrahydrofuran (100 mL). The reaction mixture was stirred at room temperature for 48 h then evaporated to dryness in vacuo and purified on silica, eluting with a gradient of solvent from dichloromethane/ethyl acetate 19:1 to dichloromethane/methanol/ammonium hydroxide 95:5:0.25. One fraction was isolated and dried in vacuo, to yield 21.53 g (66%) of the desired product as white solid. MS (m/e): 331.1 (MH+, 100%).

Source