1-Bromo-3-chloropropane → 5-(3-Chloro-propoxy)-1H-indole-2-carboxylic acid ethyl ester

HRID 901103

Reaction equation

[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([OH:15])=[CH:10][CH:9]=2)=[O:5])[CH3:2].Br[CH2:17][CH2:18][CH2:19][Cl:20].C(=O)([O-])[O-].[K+].[K+]>CC(=O)CC>[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([O:15][CH2:17][CH2:18][CH2:19][Cl:20])=[CH:10][CH:9]=2)=[O:5])[CH3:2]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of ethyl-5-hydroxyindole-2-carboxylate (15 g, 73 mmol, 1.0 eq.) and 1-bromo-3-chloropropane (8.8 mL, 88 mmol, 1.2 eq.) in 2-butanone (200 mL) was added potassium carbonate (12.1 g, 88 mmol, 1.2 eq.). The reaction mixture was stirred 160 h at 80° C. The reaction mixture was cooled down and partitioned between ethyl acetate and water. The aqueous phase was extracted with ethyl acetate. The combined organic phases were washed with water and brine then dried over sodium sulfate, filtered and concentrated in vacuo. The crude mixture was purified by column chromatography on silica eluting with cyclohexane/ethyl acetate 9:1 to yield 15.3 mg (74%) of the title compound as a light yellow solid. MS (m/e): 282.7 (MH+, 100%).

Workup

temperatureThe reaction mixture was cooled down
custompartitioned between ethyl acetate and water
extractionThe aqueous phase was extracted with ethyl acetate
washThe combined organic phases were washed with water and brine
dry with materialthen dried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude mixture was purified by column chromatography on silica eluting with cyclohexane/ethyl acetate 9:1

Sources & evidence

ORD record: ord-891340eab47746c18ea2a6b9e9b1bd4d
Source dataset: uspto-grants-2008_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07361682B2

Linked notes

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