1,3,4,9-Tetrahydro-1-ethyl-pyrano[3,4-b]indole-1-acetic Acid Ethyl Ester synthesis

Yield:111962-14-2 68%

Reaction Conditions:

with toluene-4-sulfonic acid in benzene; for 5 h;Heating / reflux;

Steps:

22.A

22.A. Synthesis of (1-Ethyl-1,3,4,9-tetrahydro-pyrano[3,4-b]indol-1-yl)-acetic acid ethyl ester A mixture OF KYPTOPHOL (1. 612 G, 10 mmol), ethyl propionylacetate (1. 730 g, 12 mmol), ANDP-TOLUENESULFONIC acid monohydrate (0.20 g) in benzene (70 mL) was heated to reflux for 5 hours. It was quenched with ethyl acetate and washed with saturated sodium bicarbonate. The organic layer was dried over magnesium sulfate, evaporated to dryness. Flash chromatography on silica gel provided 1.943 g (68%) of the title compound as a solid. MP<80 °C. 1H NMR (300 MHz, CDC13) 5 9.06 (br, 1H), 7.50 (d, 1H), 7.36 (d, 1H), 7.14 (t, 1H), 7.12 (t, 1H), 4.18 (q, 2H), 4.03 (m, 1H), 3.94 (m, 1H), 2.99 (d, 1H), 2. 88 (d, 1H), 2.78 (m, 2H), 2.14 (m, 1H), 2.01 (m, 1H), 1.25 (t, 3H), 0.82 (t, 3H) ; ESI (+) MS m/e=288 (MH+), ESI (-) MS M/E=286 (MH7).

References:

WO2005/33112,2005,A2 Location in patent:Page/Page column 73