Sodium hydride → 7-Chloro-1-[(tetrahydro-2H-pyran-4-yl)methyl]-1H-indole-3-carboxylic acid
Reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][CH:8]=[C:7]2[C:11]([OH:13])=[O:12].[H-].[Na+].[O:16]1[CH2:21][CH2:20][CH:19]([CH2:22]OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:18][CH2:17]1>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[N:9]([CH2:22][CH:19]1[CH2:20][CH2:21][O:16][CH2:17][CH2:18]1)[CH:8]=[C:7]2[C:11]([OH:13])=[O:12]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 50 °C
Procedure
To a solution of 7-chloro-1H-indole-3-carboxylic acid (7.5 g, 38.0 mmol) in dimethyl-formamide (100 ml) at 10° C. under nitrogen was added sodium hydride (60% dispersion in mineral oil, 3.1 g, 76.0 mmol) portionwise over 10 mins, maintaining the temperature below 15° C. The cooling bath was removed and the suspension stirred for 90 mins. Toluene-4-sulfonic acid tetrahydropyran-4-ylmethylester (14.6 g, 53.0 mmol) was added. The mixture was heated at 50° C. with stirring for 6 h. Dimethylformamide was removed by evaporation and the residue was dissolved in water (500 ml). The emulsion was washed with dichloromethane (2×100 ml). The aqueous phase was acidified to pH 1 using 5 M hydrochloric acid and the precipitate filtered off, washed with water to neutrality and dried to afford 7-chloro-1-(tetrahydropyran-4-yl)methyl-1H-indole-3-carboxylic acid (15.0 g, 51.0 mmol) as a white solid.
Workup
- temperaturemaintaining the temperature below 15° C
- customThe cooling bath was removed
- stirringwith stirring for 6 h
- customDimethylformamide was removed by evaporation
- dissolutionthe residue was dissolved in water (500 ml)
- washThe emulsion was washed with dichloromethane (2×100 ml)
- filtrationthe precipitate filtered off
- washwashed with water to neutrality
- customdried
Sources & evidence
- ORD record
- ord-4e3470afec584205b7a6bb7bc05214ad
- Source dataset
- uspto-grants-2010_02
- Patent number
- US07655645B2
Reaction notes
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