Potassium Carbonate → (2-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5-yl)trifluoromethanesulfonate
Reaction equation
[CH2:1]([C:5]1([CH:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)[CH2:13][C:12]2[C:7](=[C:8]([Cl:16])[C:9]([Cl:15])=[C:10]([OH:14])[CH:11]=2)[C:6]1=[O:17])[CH2:2][CH2:3][CH3:4].C(=O)([O-])[O-].[K+].[K+].[F:29][C:30]([F:36])([F:35])[S:31](Cl)(=[O:33])=[O:32]>CN(C)C=O>[CH2:1]([C:5]1([CH:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)[CH2:13][C:12]2[C:7](=[C:8]([Cl:16])[C:9]([Cl:15])=[C:10]([O:14][S:31]([C:30]([F:36])([F:35])[F:29])(=[O:33])=[O:32])[CH:11]=2)[C:6]1=[O:17])[CH2:2][CH2:3][CH3:4]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
The starting material, 2-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-5-hydroxy-1H-inden-1-one, dissolved in dimethylformamide was treated with potassium carbonate and trifluoromethanesulfonyl chloride to form (2-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5-yl)trifluoromethanesulfonate (Step 1). This material was subjected to triflate displacement by reaction with diethyl malonate to form diethyl-5-(2-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5-yl)malonate (Step 2). The malonate of Step 2 was then alkylated with ethyl 4-bromobutyrate to form diethyl 2-(2-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5-yl)-2-(ethoxycarbonyl)-1,6-hexanedioate (Step 3). Upon hydrolysis the hexanedioic acid is formed (Step 4) which undergoes monodecarboxylation by treatment with copper in quinoline to form a compound of the present invention such as 5-(2-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5-yl)pentanoic acid (Step 5). The starting materials used in these examples is obtained as shown in the Journal of Medicinal Chemistry, 20, 1400 (1977); and 21, 437 (1978). This synthetic route is illustrated below: ##STR3##
Sources & evidence
- ORD record
- ord-d6f9c0386d684527a4a82a9f079beee2
- Source dataset
- uspto-grants-1988_06
- Patent number
- US04754061
Reaction notes
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