tert-Butyl acrylate → ethyl 1-(2-tert-butoxycarbonylethyl)-4-methyl-1H-indole-2-carboxylate
Reaction equation
[CH3:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[NH:6]2.[C:16]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])(=[O:19])[CH:17]=[CH2:18].[OH-].C([N+](C)(C)C)C1C=CC=CC=1>O1CCOCC1>[C:21]([O:20][C:16]([CH2:17][CH2:18][N:6]1[C:7]2[C:3](=[C:2]([CH3:1])[CH:10]=[CH:9][CH:8]=2)[CH:4]=[C:5]1[C:11]([O:13][CH2:14][CH3:15])=[O:12])=[O:19])([CH3:24])([CH3:23])[CH3:22]Participants
Conditions
- Temperature
- 61 °C
Procedure
A mixture of ethyl 4-methyl-1H-indole-2-carboxylate (70.0 g, 344 mmol), tert-butyl acrylate (53.0 g, 413 mmol), benzyltrimethylammonium hydroxide (5.76 g, 34.4 mmol) and 1,4-dioxane (1,000 ml) was stirred at 60-62° C. for 8.5 hours. The solvent was distilled off under reduced pressure and water (1,000 ml) and acetic acid (30 ml) were added to the residue, followed by extraction with ethyl acetate (twice). The extract solution was washed with a 5% aqueous sodium hydrogencarbonate solution and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the resulting residue was crystallized from isopropanol (230 ml) to obtain ethyl 1-(2-tert-butoxycarbonylethyl)-4-methyl-1H-indole-2-carboxylate (99.2 g). M.p. 78-79° C.
Workup
- distillationThe solvent was distilled off under reduced pressure and water (1,000 ml) and acetic acid (30 ml)
- additionwere added to the residue
- extractionfollowed by extraction with ethyl acetate (twice)
- washThe extract solution was washed with a 5% aqueous sodium hydrogencarbonate solution
- dry with materialdried over anhydrous magnesium sulfate
- distillationThe solvent was distilled off under reduced pressure
- customthe resulting residue was crystallized from isopropanol (230 ml)
Sources & evidence
- ORD record
- ord-446b33a7562f44a39f4f5daeb690bc75
- Source dataset
- uspto-grants-2001_08
- Patent number
- US06271251B1
Reaction notes
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