1,4-Dioxane → 3-{(2R)-2-[2-(3-chlorophenyl)-(2R)-2-hydroxyethylamino]propyl}-1H-indole-7-carboxylic acid

HRID 1351937Notes

Reaction equation

C(N(CC)[C:4]([C:6]1[CH:7]=[CH:8][CH:9]=[C:10]2[C:14]=1[NH:13][CH:12]=[C:11]2[CH2:15][C@H:16]([NH:18][CH2:19][C@@H:20]([C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[CH:23]=1)[OH:21])[CH3:17])=[O:5])C.[O:31]1CCOCC1>Cl>[Cl:28][C:24]1[CH:23]=[C:22]([C@@H:20]([OH:21])[CH2:19][NH:18][C@H:16]([CH3:17])[CH2:15][C:11]2[C:10]3[C:14](=[C:6]([C:4]([OH:31])=[O:5])[CH:7]=[CH:8][CH:9]=3)[NH:13][CH:12]=2)[CH:27]=[CH:26][CH:25]=1

Participants

Conditions

Temperature: 150 °C

Procedure

A solution of 3-{(2 R)-2-[2-(3-chlorophenyl)-(2R)-2-hydroxyethyl-amino]propyl}-1H-indole-7-carboxylic acid diethylamide (175 mg, 0.41 mmol) in 1,4-dioxane (7 mL) and 6N hydrochloric acid (7 mL) is stirred with heating at 150° C. for 7 hours in a closed system. After cooling, the mixture is evaporated under reduced pressure to remove dioxane, and the resultant is neutralized with an aqueous Na2CO3 solution. The precipitates are filtered, and purified by reversed phase column (octa-decylsilyl, methanol/water=1/1→3/1) to give the desired 3-{(2R)-2-[2-(3-chlorophenyl)-(2R)-2-hydroxyethylamino]propyl}-1H-indole-7-carboxylic acid (45 mg, yield: 30%).

Workup

temperatureAfter cooling
customthe mixture is evaporated under reduced pressure
customto remove dioxane
filtrationThe precipitates are filtered
custompurified by reversed phase column (octa-decylsilyl, methanol/water=1/1→3/1)

Sources & evidence

ORD record: ord-46ccc422023c4242b73ea0d0a0dbc462
Source dataset: uspto-grants-2007_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07217724B2

Reaction notes

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