Etodolac → (9-Benzyl-1,8-diethyl-1,3,4,9-tetrahydro-pyrano[3,4-b]indol-1-yl)-acetic acid

HRID 268678

Reaction equation

[CH2:1]([C:3]1([CH2:18][C:19]([OH:21])=[O:20])[C:8]2[NH:9][C:10]3[C:15]([C:7]=2[CH2:6][CH2:5][O:4]1)=[CH:14][CH:13]=[CH:12][C:11]=3[CH2:16][CH3:17])[CH3:2].[H-].[Na+].[CH2:24](Br)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>O1CCCC1>[CH2:24]([N:9]1[C:10]2[C:15](=[CH:14][CH:13]=[CH:12][C:11]=2[CH2:16][CH3:17])[C:7]2[CH2:6][CH2:5][O:4][C:3]([CH2:18][C:19]([OH:21])=[O:20])([CH2:1][CH3:2])[C:8]1=2)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of (1,8-diethyl-1,3,4,9-tetrahydro-pyrano[3,4-b]indol-1-yl)-acetic acid (0.51 g, 1.8 mmol) in tetrahydrofuran at room temperature was added sodium hydride (60% dispersion in mineral oil, 0.4 g). After being heated at 50° C. for 2 hours, benzyl bromide (0.6 g, 3.5 mmol) was added and the solution was stirred for another 2 hours. It was quenched with ethyl acetate and washed with water. The ethyl acetate layer was dried over magnesium sulfate and evaporated to dryness. Flash chromatography on silica gel provided 0.486 g (73%) of the title compound as a solid. 1H NMR (500 MHz, CDCl3) δ 7.13 (m, 3H), 6.97 (d, 1H), 6.74 (d, 1H), 6.68 (t, 1H), 6.21 (d, 1H), 3.90 (s, 1H), 3.63 (m, 1H), 3.35 (td, 1H), 3.18 (d, 1H), 3.00 (d, 1H), 2.67 (q, 2H), 2.44 (q, 2H), 2.10 (m, 1H), 1.85 (d, 1H), 1.52 (m, 1H), 1.41 (m, 1H), 1.16 (t, 3H), 0.75 (t, 3H); ESI (+) MS m/e=278 (MH+).

Workup

customIt was quenched with ethyl acetate
washwashed with water
dry with materialThe ethyl acetate layer was dried over magnesium sulfate
customevaporated to dryness

Sources & evidence

ORD record: ord-ba82f5d35b844a3f8283f864b64f66fb
Source dataset: uspto-grants-2008_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07446122B2

Linked notes

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