Water → 6-chloro-7-fluoro-1H-indole-3-carbaldehyde
Reaction equation
P(Cl)(Cl)(Cl)=O.[Cl:6][C:7]1[C:15]([F:16])=[C:14]2[C:10]([CH:11]=[CH:12][NH:13]2)=[CH:9][CH:8]=1.[OH-].[Na+].O.CN([CH:23]=[O:24])C>>[CH:23]([C:11]1[C:10]2[C:14](=[C:15]([F:16])[C:7]([Cl:6])=[CH:8][CH:9]=2)[NH:13][CH:12]=1)=[O:24]Participants
Conditions
- Temperature
- 0 °C
Procedure
Add phosphorus oxychloride (0.94 g, 6.16 mmol) to DMF (12 mL, cooled in an ice bath) with vigorous stirring. After about 10 minutes, add 6-chloro-7-fluoro indole (0.93 g, 5.6 mmol) in anhydrous DMF (4 mL), stir at 0° C. for 1 hour, warm to room temperature and stir overnight at room temperature (˜16 hrs). Treat with 14.0 mL of 2N NaOH (4 eq.) with vigorous stirring. Heat the reaction to 80° C. for half an hour then cool. Pour the reaction into cold water with vigorous stirring to give a solid. Collect the solid by filtration and dry overnight in a vacuum oven at room temperature, to give the title compound: 1H NMR (300 MHz, CD3COCD3/CDCl3) 7.09 (t, 1H, J=7.7 Hz), 7.83–7.86 (m, 2H), 9.89 (s, 1H). By the method of Example 316 the following compounds were prepared: a) 3-Formyl-5,7-difluoro-1H-indole: 1H NMR (300 MHz, CD3COCD3) 6.98–7.06 (m, 1H), 7.71–7.75 (m, 1H), 8.35 (s, 1H), 10.04 (s, 1H);
Workup
- temperaturewarm to room temperature
- stirringstir overnight at room temperature (˜16 hrs)
- temperatureHeat
- customthe reaction to 80° C. for half an hour
- temperaturethen cool
- additionPour
- stirringwith vigorous stirring
- customto give a solid
- customCollect the solid
- filtrationby filtration
- customdry overnight in a vacuum oven at room temperature
Sources & evidence
- ORD record
- ord-2123edb9d93d427da971eb5c3081bbb9
- Source dataset
- uspto-grants-2007_01
- Patent number
- US07157488B2
Reaction notes
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