Dimethylformamide → 4-fluoro-3-formyl-1H-indole-7-carbonitrile
Reaction equation
[C:1](Cl)([C:3](Cl)=O)=[O:2].CN(C=O)C.[F:12][C:13]1[CH:21]=[CH:20][C:19]([C:22]#[N:23])=[C:18]2[C:14]=1C=[CH:16][NH:17]2.CCOC(C)=O>C(Cl)Cl>[F:12][C:13]1[CH:21]=[CH:20][C:19]([C:22]#[N:23])=[C:18]2[C:14]=1[C:3]([CH:1]=[O:2])=[CH:16][NH:17]2Participants
Procedure
To a solution of (COCl)2 (16.0 g) in DCM (200 mL) at 0° C. was added a solution of DMF (6 mL) in DCM (50 mL) dropwise. Half an hour later, a solution of 4-fluoro-1H-indole-7-carbonitrile (D41) (11.0 g) in DCM (60 mL) was added. The reaction was allowed to warm to RT to form a yellow precipitate. After 6 h the solvent was removed by evaporation. Then THF (100 mL) and 2M aqueous NaOH (100 L) were added to the residue obtained above. After being stirred for about 1 hour, EtOAc (1 L) was added. The organic phase was separated and the aqueous phase was extracted with EtOAc. The combined organic solution was dried over anhydrous sodium sulfate. The dried solution was concentrated to afford 4-fluoro-3-formyl-1H-indole-7-carbonitrile (D42) as a yellow solid (11.0 g).
Workup
- customto form a yellow precipitate
- customAfter 6 h the solvent was removed by evaporation
- additionThen THF (100 mL) and 2M aqueous NaOH (100 L) were added to the residue
- customobtained above
- customThe organic phase was separated
- extractionthe aqueous phase was extracted with EtOAc
- dry with materialThe combined organic solution was dried over anhydrous sodium sulfate
- concentrationThe dried solution was concentrated
Sources & evidence
- ORD record
- ord-df697b7135ed4f2ea17eb24c2e6d36aa
- Source dataset
- uspto-grants-2012_07
- Patent number
- US08217028B2
Reaction notes
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