Water → 2-Chloro-5,6,7,8,9,10-hexahydro-cyclohepta[b]indole-6-carboxylic acid methyl ester
Reaction equation
Br[CH:2]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]([C:9]([O:11][CH3:12])=[O:10])[C:3]1=O.[Cl:14][C:15]1[CH:21]=[CH:20][C:18]([NH2:19])=[CH:17][CH:16]=1.O>C(Cl)Cl>[Cl:14][C:15]1[CH:16]=[C:17]2[C:18](=[CH:20][CH:21]=1)[NH:19][C:3]1[CH:4]([C:9]([O:11][CH3:12])=[O:10])[CH2:5][CH2:6][CH2:7][CH2:8][C:2]2=1Participants
Procedure
Methyl 3-bromo-2-oxocycloheptanecarboxylate (16.8 g, 67.4 mmol) and 4-chloroaniline (18.4 g, 98%, 2.13 eq, 143.6 mmol) were added to flask with thermometer, nitrogen inlet and mechanical stirring machine. As the temperature of the mixture passed 140° C. a relatively rapid exotherm and vigorous evolution of gas occurred. The reaction was cooled with water immediately. The reaction mixture was dissolved in DCM (200 mL). The material was transferred into a separatory funnel and washed with water (2×50 mL), 3HCl (3×50 mL), water (2×50 mL), brine, dried over Na2SO4, and the solvent was removed by vacuo. The crude residue was applied to a Biotage and eluted with 9/1 heptane/ethyl acetate to afford product 10 g (53%) as an off white solid, which was used for next reaction without further purification.
Workup
- custompassed 140° C.
- customThe material was transferred into a separatory funnel
- washwashed with water (2×50 mL), 3HCl (3×50 mL), water (2×50 mL), brine
- dry with materialdried over Na2SO4
- customthe solvent was removed by vacuo
- washeluted with 9/1 heptane/ethyl acetate
Sources & evidence
- ORD record
- ord-9c741fb956784b39a8e6c58c0d9d4e26
- Source dataset
- uspto-grants-2013_07
- Patent number
- US08486990B2
Reaction notes
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