Lithium hydroxide, monohydrate → 1-(5-(2-Fluoro-5-(1-hydroxyethyl)phenyl)pyrimidin-2-yl)-3-(methylthio)-1H-indole-6-carboxylic acid
Reaction equation
O.[OH-].[Li+].[F:4][C:5]1[CH:10]=[CH:9][C:8]([CH:11]([OH:13])[CH3:12])=[CH:7][C:6]=1[C:14]1[CH:15]=[N:16][C:17]([N:20]2[C:28]3[C:23](=[CH:24][CH:25]=[C:26]([C:29]([O:31]C)=[O:30])[CH:27]=3)[C:22]([S:33][CH3:34])=[CH:21]2)=[N:18][CH:19]=1>C1COCC1.O>[F:4][C:5]1[CH:10]=[CH:9][C:8]([CH:11]([OH:13])[CH3:12])=[CH:7][C:6]=1[C:14]1[CH:15]=[N:16][C:17]([N:20]2[C:28]3[C:23](=[CH:24][CH:25]=[C:26]([C:29]([OH:31])=[O:30])[CH:27]=3)[C:22]([S:33][CH3:34])=[CH:21]2)=[N:18][CH:19]=1Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
Lithium hydroxide monohydrate (0.30 g, 7.07 mmol) was added at room temperature to a solution of 300a) (1.0 g, 2.36 mmol) in THF/water (1:1, 40 mL). The reaction mixture was stirred at this temperature for 16 h and then concentrated. The residue was diluted with water (20 mL) and washed with ethyl acetate (2×30 mL). The aqueous phase was adjusted with sodium hydrogen sulfate to a pH value of 2. The precipitating solid was filtered off through a sintered funnel and residual water was removed by azeotropic distillation with toluene. Light brown solid. Yield: 0.75 g (75% of theory)
Workup
- concentrationconcentrated
- additionThe residue was diluted with water (20 mL)
- washwashed with ethyl acetate (2×30 mL)
- filtrationThe precipitating solid was filtered off through a sintered funnel
- customresidual water was removed by azeotropic distillation with toluene
Sources & evidence
- ORD record
- ord-c7e9c886afe64f9f8318a4eb24eaf4ca
- Source dataset
- uspto-grants-2016_04
- Patent number
- US09315490B2
Reaction notes
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